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Davinder P.S. Dosanjh, DPhil; Timothy S.C. Hinks, MD; John A. Innes, MD; Jonathan J. Deeks, PhD; Geoffrey Pasvol, DPhil; Sarah Hackforth, RGN; Hansa Varia, RGN; Kerry A. Millington, DPhil; Rubamalar Gunatheesan, MD; Valerie Guyot-Revol, PhD; Ajit Lalvani, DM
Note: Drs. Dosanjh and Hinks contributed equally to this work.
Acknowledgment: The authors thank the study participants; Sarah Gooding, for collection and processing of some samples; and Muhunthan Thillai, for critical appraisal and revision of the final manuscript.
Grant Support: By the Wellcome Trust (Dr. Lalvani is a Wellcome Senior Research Fellow in Clinical Science), the Sir Halley Stewart Trust (Dr. Dosanjh's studentship), a Wellcome Trust PhD Prize Studentship (Dr. Millington), and a United Kingdom Department of Health Senior Fellowship in Evidence Synthesis (Dr. Deeks).
Potential Financial Conflicts of Interest:Consultancies: A. Lalvani (Oxford Immunotec Ltd. [nonexecutive director from 2003 to 2007]). Honoraria: G. Pasvol (Transactions of the Royal Society of Tropical Medicine). Stock ownership or options (other than mutual funds): D.P.S. Dosanjh (Oxford Immunotec Ltd.), A Lalvani (Oxford Immunotec Ltd.), University of Oxford (Oxford Immunotech Ltd.). Patents received: A. Lalvani (T-cell–based diagnosis of tuberculous infection), University of Oxford (T-cell–based diagnosis of tuberculous infection). Patents pending: D.P.S. Dosanjh (T-cell–based diagnosis of tuberculous infection), A. Lalvani (T-cell–based diagnosis of tuberculous infection, University of Oxford (T-cell–based diagnosis of tuberculous infection).
Reproducible Research Statement: The analytic data set of all participants' diagnoses, tuberculin skin test results, ELISpot results, and ELISpotPLUS results can be made available to academic investigators on request by written agreement.
Requests for Single Reprints: Ajit Lalvani, DM, Tuberculosis Immunology Group, Department of Respiratory Medicine, Faculty of Medicine, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom; e-mail, email@example.com.
Current Author Addresses: Dr. Dosanjh: University of Oxford Medical School, William Osler House, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.
Dr. Hinks: Allergy, Inflammation, and Repair Group, Level D, Southampton General Hospital, Southampton SO16 6YD, United Kingdom.
Dr. Innes and Ms. Hackforth: Department of Infection & Tropical Medicine, Birmingham Heartlands Hospital, Bordsley Green East, Birmingham B9 5SS, United Kingdom.
Dr. Deeks: Department of Public Health and Epidemiology, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
Dr. Pasvol and Ms. Varia: Department of Infection and Tropical Medicine, Northwick Park Hospital, Imperial College London, Watford Road, Harrow HA1 3UJ, United Kingdom.
Drs. Millington and Lalvani: Department of Respiratory Medicine, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, United Kingdom.
Dr. Gunatheesan: University of Melbourne Medical School, Melbourne, Australia.
Dr. Guyot-Revol: Genopoietic, 1390 rue Centrale-Beynost, 01708 Miribel Cedex, France.
Author Contributions: Conception and design: J.A. Innes, A. Lalvani. Analysis and interpretation of the data: D.P.S. Dosanjh, T.S.C. Hinks, J.J. Deeks, K.A. Millington, A. Lalvani.
Drafting of the article: D.P.S. Dosanjh, T.S.C. Hinks, G. Pasvol, A. Lalvani.
Critical revision of the article for important intellectual content: D.P.S. Dosanjh, T.S.C. Hinks, J.A. Innes, J.J. Deeks, G. Pasvol, K.A. Millington, A. Lalvani.
Final approval of the article: D.P.S. Dosanjh, J.J. Deeks, G. Pasvol, V. Guyot-Revol, A. Lalvani.
Provision of study materials or patients: J.A. Innes, G. Pasvol, S. Hackforth, H. Varia, A. Lalvani.
Statistical expertise: D.P.S. Dosanjh, J.J. Deeks.
Obtaining of funding: A Lalvani.
Administrative, technical, or logistic support: D.P.S. Dosanjh, G. Pasvol, S. Hackforth, K.A. Millington, A. Lalvani.
Collection and assembly of data: D.P.S. Dosanjh, T.S.C. Hinks, S. Hackforth, K.A. Millington, V. Guyot-Revol.
Dosanjh D., Hinks T., Innes J., Deeks J., Pasvol G., Hackforth S., Varia H., Millington K., Gunatheesan R., Guyot-Revol V., Lalvani A.; Improved Diagnostic Evaluation of Suspected Tuberculosis. Ann Intern Med. 2008;148:325-336. doi: 10.7326/0003-4819-148-5-200803040-00003
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© 2016
Published: Ann Intern Med. 2008;148(5):325-336.
Can new T-cell–based blood tests rule out active tuberculosis?
In this study involving 389 adults with moderate to high suspicion of active tuberculosis, the sensitivity of a new T-cell–based enzyme-linked immunoassay (ELISpotPLUS) was higher than that of 15-mm threshold tuberculin skin testing (89% vs. 79%) and similar to that of 10-mm threshold skin testing (83%) in unvaccinated patients for identifying culture-confirmed and highly probable tuberculosis. Patients with negative results on both ELISpotPLUS and skin tests had a very low likelihood of tuberculosis (negative likelihood ratio, 0.02).
The ELISpotPLUS assay, particularly when used in combination with tuberculin skin testing, can help exclude a diagnosis of active tuberculosis.
—The Editors
Improved diagnosis of tuberculosis is necessary to contain and reverse the rising global burden of this disease (1). The poor speed and sensitivity of existing diagnostic tools (2–4) cause delays in diagnosis and treatment of active tuberculosis, and diagnosis of extrapulmonary and paucibacillary forms is often especially challenging. Given that Mycobacterium tuberculosis infection is a prerequisite for active tuberculosis, reliable determination of infection status could accelerate diagnostic assessment by enabling rapid exclusion of tuberculosis. Recently developed T-cell–based interferon-γ release assays for tuberculosis may overcome some of the limitations of the tuberculin skin test (5–10). These immunoassays detect interferon-γ secreted by T cells in response to antigens encoded in the region of difference 1 of M. tuberculosis complex, a genomic segment absent from bacille Calmette–Guérin and most environmental mycobacteria (11). Test results are therefore not confounded by previous bacille Calmette–Guérin vaccination, conferring higher specificity than the tuberculin skin test (7–10). Moreover, results are available the next day and are unaffected by the boosting phenomenon (12).
The 2 types of T-cell–based interferon-γ release assay are whole-blood enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunospot assay (ELISpot). The whole-blood ELISA is available commercially as QuantiFERON-TB Gold and an "in-tube" variant, QuantiFERON-TB Gold In-tube (Cellestis, Carnegie, Australia) (13, 14). The ELISpot, developed by Lalvani and colleagues (15, 16), is available commercially as T-SPOT.TB (Oxford Immunotec, Abingdon, United Kingdom) (15–18). Recent U.S. and United Kingdom national guidelines (19, 20) recommend T-cell–based interferon-γ release assays for diagnosis of latent tuberculosis, but their clinical utility in evaluation of patients with suspected active tuberculosis is poorly defined.
We compared the performance characteristics of 2 assays and tuberculin skin testing individually and in combination for the diagnostic work-up of patients with suspected active tuberculosis. The standard ELISpot assay uses early secretory antigenic target-6 and culture filtrate protein-10, the same peptides as the 2 region of difference 1–encoded antigens included in T-SPOT.TB. The ELISpotPLUS assay incorporates a novel region of difference 1–encoded antigen, Rv3879c, alongside early secretory antigenic target-6 and culture filtrate protein-10 (21).
One day each week from 12 July 2002 to 29 June 2005, we prospectively enrolled adults who presented to Heartlands Hospital, Birmingham, and Northwick Park Hospital, London, United Kingdom, with suspected tuberculosis. We invited patients 16 years of age or older to participate and provide written informed consent if their attending physician considered tuberculosis to be part of the differential diagnosis. We used no exclusion criteria. The Birmingham Heartlands Hospital, Harrow, and Oxford Clinical Research Ethics Committees granted ethical approval. Because the background prevalence of HIV is low in this population (22), we tested patients for HIV antibodies during diagnostic work-up only on the basis of clinical suspicion. We identified only 20 patients who were HIV antibody–positive.
Tuberculin skin testing was performed as part of routine care, and experienced nurses read the results by using the Mantoux method with 0.1 mL (10 tuberculin units) of purified protein derivative (PPD)–Siebert (Evans Vaccines, Liverpool, United Kingdom). Intradermal inoculation was confirmed by the cutaneous appearance of peau d'orange. Induration was measured after 72 hours with a ruler and recorded in millimeters. Because PPD for Mantoux testing was unavailable for 10 months during the study period, 104 patients were tested by using the Heaf method, with the standard multiple puncture 6-needle disposable-head Heaf gun (Bignall Surgical Instruments, Littlehampton, United Kingdom) and concentrated PPD (100 000 tuberculin units/mL; Evans Vaccines). Heaf tests were read 1 week later, as recommended, and graded from 0 to 4. The nurses who performed and read skin tests were blinded to ELISpot results. We considered induration of 15 mm or greater on the Mantoux test or grade 3 or 4 on the Heaf test (which is considered equivalent to the 15-mm threshold [23, 24]) to be a positive result. We assessed bacille Calmette–Guérin vaccination status by history and, where present, by scar. We also assessed tuberculin skin test performance by using stratified cutoff points of 15 mm and 10 mm (grade 2 to 4 on the Heaf test) in vaccinated and unvaccinated patients, respectively ("stratified 10-mm threshold") (23, 24).
Before or within 1 week of initiating therapy, we obtained a sample of 30 mL of heparinized blood and used 7.5 × 106 peripheral blood mononuclear cells for ELISpot assays. We seeded precoated interferon-γ ELISpot plates (Mabtech AB, Stockholm, Sweden) with 2.5 × 105 peripheral blood mononuclear cells per well (17). Duplicate wells contained no antigen (negative control) or phytohemagglutinin (positive control) (ICN Biomedical, Aurora, Ohio) at 5 µg/mL. A further 13 pairs of duplicate wells each contained 1 of 13 peptide pools, which incorporated 5 to 7 overlapping 15-mer peptides. The assay on which T-SPOT.TB is based, defined as standard ELISpot in this study, comprises 35 such peptides assembled into 6 pools and spanning the length of early secretory antigenic target-6 and culture filtrate protein-10. Forty-five peptides from selected regions of Rv3873, Rv3878, and Rv3879c (Research Genetics, Huntsville, Alabama) were assembled into 7 pools (21). The ELISpotPLUS assay was defined as the 35 early secretory antigenic target-6 and culture filtrate protein-10 peptides, with 17 peptides from Rv3879c, assembled into 3 additional pools. The final concentration of each peptide was 10 µg/mL. After overnight incubation at 37 °C in 5% carbon dioxide, the plates were developed with preconjugated detector antibody (Mabtech AB) followed by chromogenic substrate (Moss, Pasadena, Maryland) (17). Spot-forming cells were counted by using an automated ELISpot reader (AID-GmbH, Strassberg, Germany). We predefined settings for the intensity and size of a counted spot and used the same settings throughout. We transferred mean readings from duplicate wells to a spreadsheet electronically and scored them as positive or negative by using a customized software program, ELISTAT (AID-GmbH). We scored responses as positive if test wells contained a mean of at least 5 spot-forming cells more than the mean of the negative control wells and were at least twice the mean of the negative control wells. This predefined cutoff point is the standard threshold used with our assay format in 9 studies including a total of 2506 participants (15–17, 25–30). Operators performing and reading the assays were blinded to tuberculin skin test results and personal identifiers. The ELISpot results were checked and countersigned before data entry by a scientist who did not perform the assays.
Attending physicians performed diagnostic work-up as part of routine clinical practice, which was directed on a case-by-case basis by the patient's clinical presentation. Two research nurses collected clinical, radiologic, and microbiological data on standardized forms at recruitment, during follow-up, and at final case notes review. Two physicians who were blinded to all ELISpot data assigned each patient to 1 of 4 predefined diagnostic categories (Table 1), which are similar to those used in other studies (25). Category 4 inevitably included some patients with inactive or latent tuberculosis. To compensate for heterogeneity, we further classified patients in this category into 4 predefined subgroups, analogous to American Thoracic Society classes 4, 2, 1, and 0 (31), in decreasing likelihood of latent tuberculosis (Table 1). We stratified by radiologic evidence or history of previous tuberculosis, risk factors for latent infection, and skin test results.
Table 1.
We calculated the sensitivity, specificity, likelihood ratios, and predictive values for each test and for sequences of 2 tests used in combination. Because the primary clinical utility of immune-based testing is to rule out tuberculosis, our predefined analytical plan focused primarily on sensitivities, negative likelihood ratios, and negative predictive values. We compared proportions by using Pearson chi-square and Fisher exact tests where sample sizes differed substantially (because of missing results for 1 of the tests). We compared the data from the ELISpot and ELISpotPLUS tests by using the McNemar chi-square test, treating the data as paired and dropping the 6 individuals who did not have an ELISpotPLUS result. We assumed that missing data were missing completely at random for our analyses, but we provide sufficient information for other analyses to be performed with different assumptions about reasons for missing data. Two-tailed P values are reported.
We calculated primary analyses of sensitivity, specificity, likelihood ratios, and predictive values by using categories 1 (culture-confirmed), 2 (highly probable), and 4 (active tuberculosis excluded) (Table 1). Category 3 (clinically indeterminate) cases were not included in the calculation of test performances. To investigate whether the inclusion of category 2 cases affected sensitivity, we calculated performance by using only categories 1 and 4, and to investigate whether the inclusion of categories 4A, 4B, and 4C (which included patients with latent and inactive tuberculosis) affected specificity, we calculated performance by using only categories 1, 2, and 4D (no risk factors for tuberculosis exposure).
We assessed the performance of combinations of the 2 tests by using logistic regression models. For this analysis, we necessarily restricted the data set to patients with results from both tests. Logistic regression models can be constructed in the same form as Bayesian updating (posttest odds = pretest odds × likelihood ratio) by including the log of the pretest odds of prevalence (a constant term of known value) as an offset in the model. The linear predictor then estimates log likelihood ratios rather than log odds ratios, but bootstrap methods are required to obtain valid CIs (32). We used model parameterizations from Knottnerus (33) to compute likelihood ratios for the additional diagnostic value of each test in a testing sequence, whereas we followed the recommendations of Albert (34) to obtain estimates of likelihood ratios for combinations of tests. We computed nonparametric, bias-adjusted CIs for parameter estimates from 1000 bootstrap samples.
We computed predictors of false-negative test results by using chi-square or Fisher exact tests, using the Bonferroni correction for multiple comparisons. We performed our analyses by using GraphPad Prism 4 (GraphPad Software, San Diego, California) and Stata, version 9.0 (Stata, College Station, Texas).
The Wellcome Trust had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
We enrolled 389 consenting adult patients, whose demographic characteristics are shown in Table 2. Blood was unavailable from 3 patients, tuberculin skin test results were unavailable in 67 patients, and 15 ELISpot assays (4%) were indeterminate (Figure 1). The 67 patients without tuberculin skin test results were similar to those with skin test results in terms of age, sex, ethnicity, presence of tuberculosis, site of disease, and presence of comorbid conditions (data provided on request). We classified 154 patients (40%) as having culture-confirmed tuberculosis, 40 (10%) as having highly probable tuberculosis, and 39 (10%) as clinically indeterminate; we excluded active tuberculosis in 154 patients (40%) (Table 1 and Appendix Figure 1). Twenty-eight percent of tuberculosis cases were extrapulmonary; Table 3 shows the clinical subtypes of tuberculosis and alternative diagnoses for patients without tuberculosis.
Table 2.
ELISpot = enzyme-linked immunospot assay incorporating early secretory antigenic target-6 and culture filtrate protein-10; ELISpotPLUS = enzyme-linked immunospot assay incorporating early secretory antigenic target-6, culture filtrate protein-10, and Rv3879c; TB = tuberculosis; TST= tuberculin skin testing. *Results were indeterminate because of no achievement of positive control (11 patients), high background (1 patient), peptide contamination (1 patient), inconclusive assay (1 patient), or defective ELISpot plate (1 patient). †Results were not available because of history of TB (clinically contraindicated) (45 patients), patient did not return for reading (8 patients), result not recorded (8 patients), reason unknown (3 patients), death (1 patient), test performed elsewhere (1 patient), or patient declined consent (1 patient). ‡Tuberculin skin test results were based on a 15-mm cutoff point and considered positive if induration was ≥15 mm on the Mantoux test or grade 3 to 4 on the Heaf test regardless of bacille Calmette–Guérin vaccination status.
These are the same data shown in Figure 1 but displayed in a different manner to allow scrutiny of the entire raw data set. ELISpot = enzyme-linked immunospot assay incorporating early secretory antigenic target-6 and culture filtrate protein-10; ELISpotPLUS = enzyme-linked immunospot assay incorporating early secretory antigenic target-6, culture filtrate protein-10, and Rv3879c; TB = tuberculosis; TST= tuberculin skin testing. *Results were not available because of history of TB (clinically contraindicated) (45 patients), patient did not return for reading (8 patients), result not recorded (8 patients), reason unknown (3 patients), death (1 patient), test performed elsewhere (1 patient), or patient declined consent (1 patient). †Tuberculin skin test results were based on a 15-mm cutoff point and considered positive if induration was ≥15 mm on the Mantoux test or grade 3 to 4 on the Heaf test regardless of bacille Calmette–Guérin vaccination status. ‡Results were indeterminate because of no achievement of positive control (11 patients), high background (1 patient), peptide contamination (1 patient), inconclusive assay (1 patient), or defective ELISpot plate (1 patient).
Table 3.
For culture-confirmed and highly probable cases, diagnostic sensitivities were 89% (95% CI, 84% to 93%) with ELISpotPLUS, 85% (CI, 79% to 90%) with standard ELISpot, 79% (CI, 72% to 85%) with 15-mm threshold tuberculin skin testing, and 83% (CI, 77% to 89%) with stratified 10-mm threshold tuberculin skin testing (Table 4). The ELISpotPLUS assay was more sensitive than tuberculin skin testing with the 15-mm threshold (P = 0.01) but not with the stratified 10-mm threshold (P = 0.10). The ELISpotPLUS assay was more sensitive than tuberculin skin testing with a 15-mm threshold in the 297 patients with results from both tests (89% [CI, 83% to 94%] versus 81% [CI, 73% to 87%]; P = 0.04), but not with stratified-10 mm threshold (85% [CI, 78% to 90%]; P = 0.2). The sensitivity of ELISpotPLUS was 4.2% higher than that of standard ELISpot (P = 0.02). Seven patients with active tuberculosis had ELISpot responses to novel peptides but not to early secretory antigenic target-6 or culture filtrate protein-10, of whom 4 were positive to Rv3873, 3 to Rv3878, and all 7 to Rv3879c.
Table 4.
In a sensitivity analysis to investigate whether inclusion of highly probable cases (category 2, which was biased in favor of the tuberculin skin test because a diagnosis of highly probable tuberculosis was based in part on skin test results) affected performance estimates, we reestimated sensitivity by using only culture-confirmed cases (category 1). Sensitivities were 91% (CI, 85% to 95%) with ELISpotPLUS, 87% (CI, 80% to 92%) with standard ELISpot, 79% (CI, 71% to 86%) with tuberculin skin testing using the 15-mm threshold, and 82 % (CI, 74% to 89%) with the stratified 10-mm threshold. The ELISpotPLUS assay was more sensitive than tuberculin skin testing using either the 15-mm (P = 0.005) or the stratified 10-mm threshold (P = 0.03) (Table 4).
Tuberculin skin testing and ELISpot had higher sensitivity when used in combination. For culture-confirmed or highly probable diagnoses of tuberculosis, sensitivity of ELISpotPLUS with tuberculin skin testing was 99% (CI, 95% to 100%) and standard ELISpot with tuberculin skin testing was 97% (CI, 93% to 99%) (Figure 2). A negative result on both tests was associated with likelihood ratios of 0.02 (CI, 0 to 0.09) for ELISpotPLUS with tuberculin skin testing and 0.04 (CI, 0.02 to 0.12) for standard ELISpot with tuberculin skin testing. Positive results from both tests provided likelihood ratios of 5.5 (CI, 3.2 to 9.5) for ELISpotPLUS with tuberculin skin testing and 5.7 (CI, 3.2 to 9.9) for standard ELISpot with tuberculin skin testing, whereas discordant results (likelihood ratios, 0.93 to 1.56) had no diagnostic value. Figure 2 shows sequential likelihood ratios when ELISpot assays are followed by tuberculin skin testing, and Appendix Figure 2 shows corresponding results when tuberculin skin testing is used first.
Data are for patients in whom results on both tests were available (n = 265). Except where stated, values are likelihood ratios with 95% CIs. Tuberculin skin test thresholds for positivity were induration ≥15 mm on the Mantoux test or grade 3 to 4 on the Heaf test. ELISpot = enzyme-linked immunospot incorporating early secretory antigenic target-6 and culture filtrate protein-10; ELISpotPLUS = enzyme-linked immunospot incorporating early secretory antigenic target-6, culture filtrate protein-10, and Rv3879c; TB = tuberculosis; TST = tuberculin skin testing. Top. ELISpot followed by TST. *Combined sensitivity of 1 or more positive results from tests used in combination, 97% (CI, 93% to 99%). †Combined specificity for a double-negative result from tests used in combination, 62% (CI, 53% to 71%). Bottom. ELISpotPLUS followed by TST. ‡Combined sensitivity of 1 or more positive results from tests used in combination, 99% (CI, 95% to 100%). §Combined specificity for a double-negative result from tests used in combination, 61% (CI, 52% to 70%).
Data are for patients in whom results on both tests were available (n = 265). Except where stated, numbers are likelihood ratios with 95% CIs. Tuberculin skin test thresholds for positivity were induration ≥15 mm on the Mantoux test or grade 3 to 4 on the Heaf test. ELISpot = enzyme-linked immunospot incorporating early secretory antigenic target-6 and culture filtrate protein-10; ELISpotPLUS = enzyme-linked immunospot incorporating early secretory antigenic target-6, culture filtrate protein-10, and Rv3879c; TB = tuberculosis. Top. TST followed by ELISpot. *Combined sensitivity of 1 or more positive results from tests used in combination, 97% (CI, 93% to 99%). †Combined specificity for a double-negative result from tests used in combination, 62% (CI, 53% to 71%). Bottom. TST followed by ELISpotPLUS. ‡Combined sensitivity of 1 or more positive results from tests used in combination, 99% (CI, 95% to 100%). §Combined specificity for a double-negative result from tests used in combination, 61% (CI, 52% to 70%).
The high sensitivity of the combined tests reflects the fact that false-negative tuberculin skin test results and false-negative ELISpot results occurred in different patient populations. In univariate analysis among culture-confirmed and highly probable cases, the presence of factors associated with cutaneous anergy (5) or risk for progression from latent infection to active tuberculosis (35) was associated with false-negative tuberculin skin test results (P = 0.001) but not with false-negative ELISpot results (P = 0.55). Specifically, 28% (CI, 11% to 44%) of patients with false-negative tuberculin skin test results had factors associated with cutaneous anergy (3 had diabetes and 3 were HIV-positive), compared with 5.0% (CI, 1.1% to 8.8%) of those with true-positive results. Eleven patients with tuberculosis were deemed immunocompromised on the basis of being HIV-positive (8 patients) or receiving long-term corticosteroid treatment (3 patients); 10 had positive ELISpot results and all 11 had positive ELISpotPLUS results. Neither age nor presence of any comorbid condition was associated with false-negative tuberculin skin test or ELISpot results (P > 0.11 in all cases).
The sensitivity of culture was 79% (CI, 73% to 85%) for confirmed and highly probable tuberculosis, which was lower than that of both ELISpot assays; this difference was significant for ELISpotPLUS (P = 0.005). Microscopy had a sensitivity of 39% (CI, 32% to 46%). Microbiological techniques had lower sensitivity in extrapulmonary disease than in pulmonary disease (culture, 53% [CI, 39% to 67%] vs. 89% [CI, 83% to 94%], respectively [P < 0.001]; microscopy, 14% (CI, 5.5% to 26%) vs. 49% (CI, 40% to 58%), respectively [P < 0.001]), whereas ELISpotPLUS had nonsignificantly higher sensitivity in extrapulmonary disease (94% [CI, 84% to 99%]) than in pulmonary disease (88% [CI, 81% to 93%]) (P = 0.19). Among patients with suspected pulmonary tuberculosis, the sensitivity of sputum microscopy with ELISpotPLUS was 94% (CI, 89% to 98%) for culture-confirmed and highly probable cases, generating a negative likelihood ratio of 0.10 and a negative predictive value of 90%, compared with a sensitivity of 78% (CI, 69% to 85%) for microscopy combined with tuberculin skin testing (P < 0.001).
Specificity of ELISpotPLUS was 69% (CI, 61% to 77%) for active disease in all category 4 patients, which was lower than the specificity of tuberculin skin testing (81% [CI, 73% to 87%]; P = 0.03). Although ELISpotPLUS gave more diagnostic negative likelihood ratios and negative predictive values than tuberculin skin testing, positive likelihood ratios and positive predictive values were somewhat lower, most likely because of detection of latent infection in category 4 patients; this finding is consistent with the 84% (CI, 60% to 97%) specificity of ELISpotPLUS calculated by using category 4D patients (who were considered least likely to have latent infection). The specificity of standard ELISpot was similar to that of ELISpotPLUS (Table 4). Three of 21 category 4D patients had false-positive results by standard ELISpot, and 3 of 19 had false-postive results by ELISpotPLUS. All 3 individuals who had false-positive ELISpotPLUS results were United Kingdom–born white persons with 0 mm of induration on the Mantoux test, and 2 were 75 years of age or older. Only 2 category 4D patients who were negative by standard ELISpot were positive to any of the new antigens; both responded to Rv3873 alone. Thus, inclusion of Rv3879c alone in ELISpotPLUS enhanced diagnostic sensitivity without compromising specificity.
Our comparison of the Heaf test and the Mantoux test with a 15-mm induration threshold for patients with culture-confirmed and highly probable cases of tuberculosis revealed a nonsignificant increase in sensitivity for the Heaf test (86% [CI, 74% to 82%] for the Heaf test vs. 76% [CI, 66% to 84%] for the Mantoux test; P = 0.14) and a higher specificity for the Mantoux test (66% [CI, 46% to 82%]) for the Heaf test vs. 85% [CI, 77% to 92%] for the Mantoux test; P = 0.02) (subgroup data provided on request). Receiver-operator characteristic analysis indicated that the area under the curve for both skin test formats was identical at 0.84. Subgroup analysis of combined use of standard ELISpot or ELISpotPLUS followed by Mantoux testing (for the 184 patients who received Mantoux testing) gave similar final likelihood ratios to those observed in the whole study population tested with Mantoux or Heaf methods (265 patients; subgroup data provided on request).
Overall, 4.7% of positive results on standard ELISpot or ELISpotPLUS were dependent on a single peptide pool response of 5 to 10 spot-forming cells per well. These results might be considered borderline positive.
This prospective study has defined a role for T-cell–based interferon-γ release assay testing in the diagnostic evaluation of patients with suspected tuberculosis. The 89% sensitivity of ELISpotPLUS for a diagnosis of culture-confirmed or highly probable tuberculosis was higher than that of the standard ELISpot, tuberculin skin testing, and culture. The combined sensitivity of ELISpotPLUS and tuberculin skin testing in confirmed and highly probable cases was 99%.
The negative likelihood ratio of 0.15 with ELISpotPLUS means that a negative result would reduce the odds of tuberculosis by 6.5-fold, which allows it to be used as a rule-out test in patients with a moderate or low pretest probability of tuberculosis. Given the high pretest probability of tuberculosis (0.50) in our patient population (patients attending urban infectious disease units), the negative predictive value of ELISpotPLUS alone was modest at 83%. However, the 99% combined sensitivity of tuberculin skin testing and ELISpotPLUS and the corresponding negative likelihood ratio of 0.02 allow the combined use of these assays as a rule-out test for tuberculosis, even in populations with high pretest probabilities, such as our study sample. Pretest probabilities in other settings, such as general medical or primary care clinics in low-prevalence countries, will be much lower, and the negative predictive value of ELISpotPLUS, alone or in combination with skin testing, will be correspondingly higher. The higher sensitivity of ELISpotPLUS compared with standard ELISpot was entirely attributable to the addition of 1 antigen, Rv3879c (to which Rv3873 and Rv3878 provided no further incremental sensitivity), which supports inclusion of Rv3879c in T-cell–based interferon-γ release assays.
Analysis of tuberculin skin testing using the lower 10-mm induration threshold in patients not vaccinated with bacille Calmette–Guérin showed a nonsignificant increase in sensitivity and decrease in specificity. Whereas ELISpotPLUS was not significantly more sensitive than skin testing with the stratified 10-mm threshold in patients with confirmed and highly probable tuberculosis, it was significantly more sensitive in the patients with culture-confirmed disease. This is probably because the diagnosis of highly probable tuberculosis was based in part on skin test results, which biases results in favor of the skin test.
Our results are probably generalizable to clinical units evaluating patients with suspected tuberculosis in other low-prevalence countries because we performed our study in routine clinical practice and included a wide spectrum of clinical cases and alternative diagnoses (36, 37). This may also account for the lower sensitivity of standard ELISpot in our study compared with earlier, smaller studies of more selected patient groups (16, 18, 38). Because our population comprised relatively few immunocompromised patients, our results cannot be generalized to populations with a higher prevalence of HIV co-infection, although previous studies of larger numbers of patients with tuberculosis who were co-infected with HIV suggest that ELISpot has high sensitivity in this group (25, 28). Our study population was predominantly South Asian and black; further studies are required in other ethnic groups. Results will be less generalizable outside low-prevalence countries, because the utility of ELISpot in endemic regions will be limited by higher background rates of latent tuberculosis (29, 39). This reduces the utility of a positive result; however, negative results (although proportionally fewer) would still be useful to rule out a diagnosis of tuberculosis (8, 25, 40).
Any T-cell–based test with a high sensitivity for M. tuberculosis infection will detect latent infection in patients who are suspected of having tuberculosis but in whom active tuberculosis has been excluded. Because our study population predominantly comprised patients with suspected tuberculosis from ethnic groups with a high prevalence of tuberculosis and latent tuberculosis, patients without active tuberculosis had a much higher risk for latent infection than would healthy control patients selected for very low risk for infection. This explains the 66% to 86% specificities of ELISpot and tuberculin skin testing when used as markers of active tuberculosis. Hence, when used to support a diagnosis of active tuberculosis, immune-based tests of infection should be interpreted in the context of the overall clinical picture and diagnostic work-up (40), as is recognized for tuberculin skin testing.
Given that culture remains the diagnostic gold standard and is required for identifying drug resistance, we believe our findings will have the following effects on clinical decision making. First, a negative ELISpotPLUS result can assist in excluding tuberculosis when the pretest probability is low-to-moderate. When pretest probabilities are higher, combined use of ELISpotPLUS and tuberculin skin testing excludes tuberculosis with a greater degree of certainty (Figure 2). The likelihood ratio of 0.02 to 0.04 refines a pretest probability of 50% to a posttest probability of approximately 2% (41) in patients with double-negative results, who constituted more than one quarter of those tested in our study. Conversely, a positive ELISpotPLUS (or standard ELISpot) result with a corresponding likelihood ratio of 2.8 is of limited value. However, in patients with positive results on both ELISpot and the tuberculin skin test, who constituted nearly one half of those tested, the corresponding likelihood ratio of 5.5 increased the probability of active tuberculosis by approximately 30% (41). Thus, double-positive results may help guide decisions about early initiation of presumptive treatment in severe disease while awaiting culture results and in extrapulmonary disease, in which culture is frequently negative. Combined testing also generates some discordant results (Figure 2). In these cases, which amounted to one quarter of persons tested, the near-unity likelihood ratios do not alter pretest probabilities and do not contribute to the diagnostic work-up.
The rate of indeterminate ELISpot results in our study was similar to the 3% to 4% rates observed in other studies (42, 43) and less than the 11% to 21% rates observed with whole-blood ELISA in routine practice (42, 44). Indeterminate ELISA results are associated with immunosuppressive therapies or conditions (42, 44), but no such association was seen for ELISpot in this or other studies (25, 42, 43, 45, 46). Moreover, the proportion of patients with tuberculosis was no higher among those with indeterminate results. As expected, false-negative skin test results were associated with factors known to cause anergy or progression to active disease. These factors did not confound the ELISpot results, consistent with previous findings (10, 15, 42).
The 99% combined sensitivity of tuberculin skin testing and ELISpot reflects the fact that patients who had a false-negative result on one test were distinct from those who had a false-negative result on the other. This implies that distinct immunologic processes underlie failure of these different, yet complementary, immune-based tests.
The main weakness of our study arises from the problem of differing standards for tuberculin skin testing. Standards vary worldwide, differing by type of tuberculin, production standards, method of administration, dose, and skin test cutoff points (13, 23, 24, 31, 35, 47). Where possible, we used a 10–tuberculin unit PPD–Siebert Mantoux test (in accordance with the United Kingdom standard at the time) and corresponding cutoff points for induration. In one quarter of patients, a Heaf test was used for logistical reasons. When standard thresholds for Mantoux test equivalence were used (23, 24), the Heaf test showed a nonsignificant increase in diagnostic sensitivity and a significant decrease in specificity relative to the Mantoux test. Subgroup analysis of patients who had Mantoux testing showed that conclusions for combined testing with ELISpot or ELISpotPLUS followed by Mantoux testing were similar to those for the study population as a whole. Parallel testing with the alternative whole-blood ELISA T-cell–based interferon-γ release assay would have been of interest, but neither this test nor the T-SPOT.TB (which is based on the standard ELISpot used here) was available when our study began. The modest sample size, limited number of immunocompromised patients, and lack of a definitive gold standard are also limitations of our study. Because many patients with tuberculosis are culture-negative (48), a microbiological gold standard used alone is too insensitive to evaluate new diagnostic tests. We therefore included highly probable cases in our composite reference standard, which better reflects the clinically relevant population, and our sensitivity analysis confirmed that estimates based on the composite reference standard were similar to those based on the microbiological reference standard. Finally, because this is only the second study to evaluate Rv3879c (21) and the first prospective study, further validation of its incremental sensitivity is required.
In summary, we found that ELISpotPLUS was a sensitive and clinically useful diagnostic test for evaluation of patients with suspected tuberculosis. Incorporation of a novel antigen, Rv3879c, conferred improved sensitivity over standard ELISpot. Combined use of tuberculin skin testing with either ELISpotPLUS or ELISpot enabled rapid exclusion of tuberculosis in patients with moderate to high probability of infection.
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Liu Hong
Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University
March 15, 2008
The application strategy of tuberculin skin testing, ELISpotPLUS and ELISpot
To the editor:
We read with interest the article by Dosanjh and colleagues (1). They clearly show that ELISpotPLUS is a sensitive and clinically useful diagnostic test for evaluation of patients with suspected tuberculosis. However, they don¡¯t show the cost effectiveness of ELISpotPLUS versus tuberculin skin testing and ELISpot. Clinicians will need to know which assay is recommended for wide clinical application. Could the authors comment on the application strategy of the three assays, including separate application and combined application?
This study is based on the participants predominantly in South Asian and black ethnicity, so the results may not be applicable for all patients with suspected tuberculosis. Will incorporation of Rv3879c improve sensitivity over standard ELISpot for all patients? Could the authors comment on the potential effect of epigenetic inheritance on the roles of Rv3879c, which is regulated by a special molecular network? So it is indispensable to ask whether the molecular network involve other important antigens for the clinical diagnostic evaluation of suspected tuberculosis.
1. Dosanjh DP, Hinks TS, Innes JA, et al. Improved Diagnostic Evaluation of Suspected Tuberculosis. Ann Intern Med. 2008 Mar 4;148(5):325-36.
None declared
David M. Brett-Major
Division of Infectious Diseases, National Naval Medical Center, Bethesda MD
March 17, 2008
No Title
No Comment
Ivan Landires
Institut Pasteur, UP Pathogénomique Mycobacterienne Integrée, Paris, France
April 2, 2008
Can IFN Gamma Release Assays Differentiate Between Active Tuberculosis and Sarcoidosis ?
Dear Editor,
We have read with great interest the recent article by Dosanjh and colleagues (1) who found that the ELISpotPLUS assay was a clinically useful diagnostic test for evaluation of patients with suspected tuberculosis. This assay uses an additional region of difference 1""encoded antigen, Rv3879c, alongside early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10, which are all part of the recently identified, novel ESX-1 secretion system of Mycobacterium tuberculosis (2).
As mentioned in the editorial (3), the use of these tests for the diagnosis of active tuberculosis is based on the logic that one must have tuberculous infection in order to have tuberculosis disease. But, is the ELISpotPLUS assay able to establish a differential diagnosis between active tuberculosis and sarcoidosis? M. tuberculosis has been proposed as a candidate trigger for the development of sarcoidosis and several mycobacterial antigens have been recovered from sarcoidal tissue (4). Recent studies have detected Th-1 immune responses to M. tuberculosis ESAT -6 using the ELISpot assay in sarcoidosis patients (5). A diagnosis of sarcoidosis is firm when chest radiographic evidence is accompanied by compatible biopsy and characteristic clinical features, with all other causes of granulomas ruled out (4). For that reason it will be important to evaluate ELISpotPLUS responses to ESX-1 peptides in sarcoidosis patients and compare these findings with ELIspotPLUS results from patients with active tuberculosis. Overall, we suggest that this issue merits further investigation.
1. Dosanjh DP, Hinks TS, Innes JA, Deeks JJ, Pasvol G, Hackforth S, et al. Improved diagnostic evaluation of suspected tuberculosis. Ann Intern Med. 2008; 148: 325-36.
2. Brodin P, Rosenkrands I, Andersen P, Cole ST, and Brosch R. ESAT-6 proteins: protective antigens and virulence factors? Trends Microbiol. 2004; 12:500-508.
3. Menzies D. Using tests for latent tuberculous infection to diagnose active tuberculosis: can we eat our cake and have it too? Ann Intern Med. 2008; 148: 325-36.
4. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007; 357: 2153-65.
5. Drake WP, Dhason MS, Nadaf M, Shepherd BE, Vadivelu S, Hajizadeh R, et al. Cellular recognition of Mycobacterium tuberculosis ESAT-6 and KatG peptides in systemic sarcoidosis. Infect Immun. 2007; 75: 527-30.
Infectious Disease, Mycobacterial Infections.
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Hickory Veterinary Hospital, located in the Great Bridge section of Chesapeake, Virginia is a full-service Veterinary Hospital offering high quality medicine, surgery, dentistry, Acupuncture and Eastern Medicine for dogs, cats, pocket and exotic pets.
Dr. Jerry Redding and Dr. Jeff Klemm welcome you to Hickory Veterinary Hospital and look forward to making you and your pet part of the Hickory Veterinary family. From routine wellness visits to high-tech laser surgery, our veterinarians provide top-notch care to our veterinary client family.
Check out our blog for information on past events and other educational health articles for you and your pet.
Food Therapy is one of the central treatment modalities in Traditional Chinese Veterinary Medicine (TCVM). In simple terms, it is the art and science of using selected food ingredients to rebalance the body's energies.
Food therapy, like acupuncture and Chinese herbal medicine, can be combined with and compliment traditional western medicine to treat a wide variety of acute and chronic illnesses, and to promote the overall well-being of your pet.


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It hardly feels like the first of November with temperatures that started off in the lower 70s this morning!{ } Big changes ahead, though.{ } A strong cold front is sliding through and will drop temperatures through the weekend.{ } Showers chances will taper off through the afternoon, but a little rain could linger over southern MD through the evening, as the front stalls a bit.{ }
The weekend will be mainly dry, breezy, and cooler.{ } Clouds will build in tomorrow afternoon with seasonable highs in the mid 60s.{ } Sunday will be even cooler, with highs in the mid to upper 50s with abundant sunshine.


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RARITAN TWP. â Township police would receive 2.3% raises for each year of their new three-year contracts, which cover 2013, 2014 and 2015, if the Township Committee approves the necessary ordinances tomorrow, June 18.
But the salaries for rookies would come down dramatically. A new recruit hired in 2012 was paid $55,947 to start, rising to $57,724 after the six-month training period. The new schedule gives the same starting salary all three years â $40,000, with no raise at the six-month point. According to the schedule in the ordinance it would only take them 19 years to reach the top, instead of 24 years for cops hired 1997-2012.
The top pay for a patrolman in 2013 is $107,551, which is achieved after 20 years by patrolmen hired before 1997.
âLongevity was eliminated for all,â said Township Administrator Allan Pietrefesa. âCurrent employees had the longevity rolled into their base pay.â
A sergeantâs pay for 2013 would range from $110,526 to $119,368; and a lieutenantâs pay would range from $130,116 to $135,321.
These salary schedules are contained in two ordinances â one for patrolmen negotiated by PBA Local 337; and one for sergeants and lieutenants negotiated by the Superior Officers Association of PBA Local 337A. There will be a public hearing on each ordinance, probably with a vote on final passage afterward.
The Township Committee meeting will be held in the Municipal Building just off the Dvoor circle. The meeting starts at 7 p.m.
More Hunterdon County news: NJ.com/hunterdon ⢠Facebook ⢠Twitter


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Of all the various articles previewing Team USA's Olympic selection camp, which begins today in Chicago, only one Red Wings-related storyline stands out--and, as Al Muir notes, it's a matter of "experience" leading a youthful group of players:
August 17, Sports Illustrated: The 34-boy, er, man roster compiled for this camp by GM Brian Burke and his staff includes just four returnees (Mike Modano, Chris Drury, Scott Gomez and Brian Rafalski) from the 2006 squad that finished a dismal eighth in Turin. A fifth player, Jamie Langenbrunner, has experience from the 1998 team. Of that group, only the 35-year-old Rafalski is likely to play a major role when the Yanks take on the Swiss at Vancouver's GM Place in the tournament opener next year.
Yahoo Sports' Ross McKeon points out that the U.S. is relatively inexperienced on the blueline, magnifying Rafalski's importance to the team:
August 16, Yahoo Sports: On defense, it's a vastly different group from years past - and this is where the Americans will be challenged. Detroit's Brian Rafalski is the senior member of the group that includes Pittsburgh's Brooks Orpik, New Jersey's Paul Martin, Los Angeles' Rob Scuderi, Toronto's Mike Komisarek, Anaheim's Ryan Whitney, Edmonton's Tom Gilbert and Atlanta's Tim Gleason, among vets. Los Angeles' Jack Johnson, St. Louis' Erik Johnson and Nashville's Ryan Suter hope to open some eyes.
The Sporting News's Ray Slover goes so far as to suggest that Rafalski will garner an Alternate/Assistant Captain's "A," and I definitely agree there.


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How To Create 14 Sparkly Craft Projects Using Krylon Glitter Blast
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Sweet Treat Partyware
By: Tiffany Windsor for www.cool2craft.com
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With this easy reverse decoupage technique from Tiffany Windsor, you can create the sweetest custom partyware and matching napkins. Create your own fabulous glassware for entertaining.
- Sizzix Bigz Die – Vine w/Leaves & Fruit (#656532)
- Sizzix Bigz Alphabet Die Set – Go Slim Lowercase (or alphabet dies of your choice)
- Scrapbook papers
- Zip-Dry Glue by Beacon
- Mod-Podge by Plaid – Matte finish
- Clear glass plates and clear glass tray
- Acrylic paint – gold or color of choice
- Paint brush
- Cloth napkins
- Iron-on fusible web
- Iron
- Wash and thoroughly dry plates and tray to remove any fingerprints. Set aside.
- Die cut alphabet letters, vines and fruit from paper. Measure and cut paper to fit exactly on back of tray and center circle of plates. (For the tray, you may need to use a full sheet of 12x12 plus several strips of paper to cover the entire back.)
- To create dessert plate, determine placement of vines, leaves, fruit and lettering and glue in place with Zip-Dry. Let dry completely.
- Brush Mod-Podge onto center circle on back of plate (you are creating a reverse decoupage). Brush Mod-Podge glue onto front of paper (brushing over entire glued design). Press face down onto back of plate and use your fingers to gently rub paper to secure onto plate. Turn plate over and check to be sure that you rub around the glued designs pressing glue into all crevices. When Mod-Podge dries, it is clear but be sure that you have a smooth even coat. Next, apply a smooth coat of Mod-Podge to the back of the paper, paying attention to secure edges of paper completely. Let dry. Brush coat of acrylic paint over back of paper. Let dry.
- Repeat technique for each plate and tray.
- For napkins, iron fusible web onto back of fabric. Die cut designs. Remove backing paper and iron onto napkins.
Designer Note:
- Because you have sealed the paper with the glue and acrylic paint, this glassware is hand-washable. Just clean with damp sponge and dry thoroughly. Enjoy the ooh's and aah's at your next tea party!
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Ex-POWs visit Brooke museum
WELLSBURG – Members of the Ex-Prisoners of War Barbed Wire Chapter toured the Brooke County Museum and Cultural Center Wednesday and learned about efforts to collect local veterans' stories in a book series.
Chartered in 1974, the group is comprised of former POWs from Hancock, Brooke, Ohio and Belmont counties who meet monthly for camaraderie and have spoken to students and other groups.
Its leader is John Chernenko of Wellsburg, a former U.S. marshal and state senator who was captured by German troops while fighting in the Battle of the Bulge.
During the group's business meeting, another visitor, Marilyn McCord, noted the museum board is planning a book featuring short profiles of veterans living in Hancock, Brooke and Ohio counties.
The project was inspired by the "Marshall County Patriots and Heroes" series produced by Gary Rider, an author and former teacher, and his wife, Patty. In its fourth volume, the book series has compiled the stories of hundreds of Marshall County veterans.
Ruby Greathouse, museum volunteer curator, said the veterans will be asked to share special stories of their military experience and briefly describe their civilian lives afterward and how their military service affected them.
She added the group will be raising funds to print the book and will accept donations in honor or memory of a veteran. Plans call for such contributions to be acknowledged in the book.
Veterans interested in being featured in the book may obtain information forms at the Brooke County Courthouse or libraries in each county, by calling (304) 312-5316, e-mailing firstname.lastname@example.com or writing to: Military Heroes Project, 704 Charles St., Wellsburg, WV 26070.
The former POWs also heard from Del. Phil Diserio, D-Brooke, who shared legislation involving veterans, from the requirement that all state facilities fly the POW-Missing in Action flag daily to the planned construction of an assisted living facility for veterans in Beckley.
Following the business meeting, the group toured the museum, including two rooms dedicated to military service and conflicts involving Brooke County residents dating from the American Revolution to Iraq and Afghanistan.
Among the many items displayed are World War II-era military uniforms worn by local residents; copies of a 1940s Weirton Steel bulletin listing employees in the military and containing photos of many of them in uniform; a photo of Isaac P. Duval, a Union Army genera; and half of a Union flag that belonged to him.
Paul "Bud" Billiard donated to the museum several items belonging to his uncle, Steven J. Spataro, who was a radio man in the Army Air Corps, a predecessor to the Air Force, who was killed in 1942 when complications during a training maneuver caused his plane to go down.
Greathouse said it wasn't unusual for officers in a Union regiment to divide the flag into pieces for souvenirs.
In addition to Chernenko, POWs who visited the museum included Pete Lallone of Wellsburg, who also was captured during the Battle of the Bulge; Dave Dean of St. Clairsville, a retired Air Force major who was aboard a bomber plane when it was shot down over Germany; Boyd Engle of Glen Dale, who was an assistant tank driver when he was captured in Italy during World War II; and Bill Daniel of Wheeling, who was in an Army infantry unit that faced the guns of a German tank before he was captured during the war.
Located at 704 Charles St., the museum is open from noon to 5 p.m. Thursdays, Fridays and Sundays. Arrangements for visits at other times also may be arranged by calling (304) 737-4060 or (304) 312-5316.
(Scott can be contacted at firstname.lastname@example.com)


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Anybody else get this in their head while doing the Blends project?
For those of you who don't have a first grader at my kid's school, the Blends Project is 30% of their grade. Basically, the teacher gives you a list of 20 "blends" – blends are letter combinations, such as "br" and "ch." The kids have to come up with four words for each blend (CH: Choir, Chorus, Chorizo, Chair). Then, the kids have to draw or cut out pictures representing each of the words. Each cutout must be of a size that it will fit into one fourth of one 20th of a large piece of poster board. Confused? Yeah, the kids are supposed to divide their poster board into 20 equal parts, and each of those parts will contain four pictures. The pictures are then labeled with the name of the word they represent.
Note that I say "the kids" are supposed to be doing all of this. As if kids in first grade can do all of this. Me? I am lucky, in that my kid learned all his blends two to three years ago, so he had no problem coming up with his own words. (Don't even get me started on the fact that they are not differentiating this project at all for the kids who are strong readers and already know their blends.) Other parents are not so lucky – they have to help their kids figure out four words for each blend.
What ends up happening is that the parents then go to the computer and google clipart that corresponds to the word. Then they print it all out for the kid to cut out. Then the parent has to divide the squares on the poster board. (I mean, come on! How many first graders could figure that out?)
So, basically, if the kids don't know their blends yet, then the parents end up doing half the work. Even for my kid, who knows his, I end up having to do the clip art portion (took me TWO HOURS last night to google, and cut and paste, and print, the 80 images.) The plus to this is that Rollie and I spent some quality time together. By quality time, I mean that he and i did the images, while Tiller cried under the computer desk, rolling around at my feet, wailing about how bored she was, and I didn't finish my laundry.
A negative to this whole thing might be that my son did not learn a DAMN thing. Oh! Except for the following "enlightening" images that came up while searching for words he already knew how to spell.
Interesting things that come up on Google Images while searching for pictures of words for Blends project:
drug (people smoking pot, shooting heroin, laying passed out next to an open and spilled bottle of pills with a bottle of bourbon in hand, pot leaf, bong, bag of weed, cartoons with needles hanging out of people's arms.)
brown (pile of poop, naked African American woman, James Brown mugshot)
Drown (pictures of drowning victims, scary illustrations of drowning people)
Drink (OH GOD, Alt+Tab!)
frenzy (wolves tearing apart some animal, creepy cartoons with people foaming at the mouth, zombie melee)
prank – (one KKK poster, a rear end mooning the camera)
glowstick (rave photos, symbols of hands holding glowsticks up in the air, Rollie: "What's a rave?")
spank (Are you kidding me? Me: Don't you want to pick another word? That one is kind of negative. Rollie: Why? It's just hitting on the bottom? Me: sigh. Ok. [praying as i hit google], Oh, no, that one is not good. Rollie: Mama, what is? Me: Don't worry about that one, honey.)
spa (who knew there were so many asian "spa" pictures online?)
blonde? (I don't even need to describe what came up for this one, right?)
Slip (lots of disturbing photos and cartoons about the band slipknot. R: Mama, what is a slipknot? Me: A kind of knot. R: For putting around your neck?)
Gee. Education is great.


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Looking for a three-game sweep, Washington sends Stephen Strasburg (8-10, 3.68 ERA) to the mound Thursday night against Dillon Gee (4-4, 3.54), who is 7-3 with a 3.23 ERA in 13 career starts against the Nationals.
Mets: RHP Matt Harvey (elbow) threw 27 pitches during a bullpen session at the team's complex in Port St. Lucie, Florida. ... RHP Daisuke Matsuzaka (right elbow inflammation) is scheduled for another rehab outing Saturday with Double-A Binghamton.
Mets star David Wright extended his hitting streak to 12 games with a first-inning single. But the crowd groaned as he tried to stretch it to a double and was thrown out easily by Frandsen, who also made a sliding grab on Wright's drive in the sixth.


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[Women at a cemetery in Kabul, picture by Reuters' Ahmad Masood]
As U.S. President Barack Obama makes up his mind on comitting more troops to Afghanistan, the search for analogies continues. Clearly, Afghanistan cannot be compared with Vietnam or Iraq beyond a point. The history, geography, the culture and the politics are just too different.


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New Jersey is getting out of the highway sound wall business for now.
''It is unfortunate, but for the foreseeable future, there will not be sufficient funds available to allow us to advance funding for noisebarrier projects,'' Jennifer D. Godoski, deputy commissioner for the New Jersey Department of Transportation, wrote in a letter this month to Somerset County freeholders.
The DOT officially rejected a proposal to construct sound barriers along Route 78 in the Bridgewater-Watchung corridor. The noise walls would have cost around $3.5 million.
Instead, the department proposes to alleviate some of the noise this month with a new type of ''quiet pavement'' that is a mixture of hot asphalt and crumb rubber derived from waste or scrap tires.
Formally known as asphalt rubber open graded friction course, the environmentally friendly pavement provides excellent durability, skid resistance, ride quality and improved wet weather visibility, Godoski noted.
The department is also planning to plant vegetation by the end of this spring on westbound Route 78 in the Bridgewater-Watchung corridor, providing an ''evergreen screen'' to soften the effect of highway noise for older residential houses.
The last stand-alone noise wall in New Jersey was built along Route 80 in Totowa at the end of 2005 and cost around $2.2 million, the DOT's Tim Greeley said.
The state's noise mitigation program has investigated noise levels in communities where highways were built prior to the National Environmental Policy Act of 1969, according to the DOT.
Because it has been more than a decade since the sound barrier proposal was on the front burner in Somerset County, the reaction in some local circles was, ''What wall?''
''Some of the local officials weren't even aware that walls were supposed to be built,'' county Freeholder Peter S. Palmer said.
Palmer, who with 13 years served is the senior freeholder on the board, said the plan to build noise walls predated even his time on the board.
Palmer, the Somerset freeholder liaison on the North Jersey Transportation Planning Authority, said he couldn't recall neighbors asking for the walls in recent years.
Still, he said, ''I'm sure they'd like to have less noise.''
There will be no sound walls in the foreseeable future, but roadwork is still getting done on Route 78. Under discussion is a plan to build a ramp at exit 43 of Route 78 to allow westbound drivers on 78 to go on Diamond Hill Road toward Scotch Plains instead of having to go up a hill in Berkeley Heights and turn around in a neighborhood, which Palmer called ''a real hassle.''
And moving forward is a plan is to add an extra lane to the ramp from southbound Route 287 to westbound 78, which gets clogged at night with commuters returning home to western New Jersey and eastern Pennsylvania, Palmer said.
But at $5 million per mile, highway sound walls are not part of the current discussion in New Jersey.
''As our infrastructure ages and construction costs continue to escalate, the level of funding allocated to maintaining a safe and efficient transportation network has not kept pace with needs,'' Godoski wrote. ''Recently, the NJDOT has been forced to make very difficult decisions on how best to utilize the limited funds that are available. Projects to mitigate roadway noise compete directly with projects that are being developed to improve safety on our roads, reduce congestion, repair aging bridges, and to repair roadway infrastructure.''


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1. 'Dreadful' season finale
Showtime's "Penny Dreadful" re-imagines a 19th-century London where Mina Harker from "Dracula" and Victor Frankenstein and his monster roam the streets. The horror series' first season has only eight episodes, so the tale of Timothy Dalton as Sir Malcolm Murray, an explorer searching for his kidnapped daughter Mina, reaches its season finale at 10 p.m. Sunday, June 29.
2. The Bard at Stan Hywet
The Ohio Shakespeare Festival performs Shakespeare's "Twelfth Night" at Stan Hywet Hall and Gardens this summer. The play opens Thursday, July 3 and runs Thursdays, Fridays, Saturdays and Sundays through Sunday, July 20. Curtain time is 8 p.m.; grounds open at 6 p.m. for picnics. $15-$30, 714 N. Portage Path, Akron.
3. Fireworks and music
The Brooklyn Bridge will serve as a dramatic stage for dazzling fireworks during the 38th annual "Macy's 4th of July Fireworks Spectacular" live television special. "America's Got Talent's" Nick Cannon hosts the show, which includes performances by Ariana Grande, Hunter Hayes, Miranda Lambert and Lionel Richie. "Macy's 4th of July" airs 8 to 10 p.m. Friday, July 4, and will be repeated at 10 p.m. on WKYC Channel 3.
4. Revealing new CD
Pop culture watchers can't wait to hear Robin Thicke's new CD, "Paula," to see if it's part of Thicke's campaign to woo back his estranged wife, actress Paula Patton. Here's a big hint: the lead single is called "Get Her Back." Give a listen when "Paula" ($13.99) hits stores Tuesday, July 1.
5. Funny husband and wife
Melissa McCarthy is sleeping with the director of her new movie — but it's OK, he's her husband. McCarthy and husband Ben Falcone collaborated on her summer comedy, "Tammy"; they co-wrote the script and Falcone directs and appears in the movie. Tammy (McCarthy) is broke but determined to hit the road to escape her crappy life. Lacking a car and cash, her only option is to take along her grandmother Pearl (Susan Sarandon). Look for Kathy Bates and Allison Janney in the cast. Opening Wednesday, July 2.
6. Back inside the 'Dome'
Expect more evil doings from Big Jim (Dean Norris) on "Under the Dome,", when the horror-thriller returns for a second season at 10 p.m. Monday, June 30, on WOIO Channel 19. The CBS series, based on a Stephen King novel, is about a small town mysteriously cut off from the rest of the world by an impenetrable dome.
7. World belongs to apes
Matt Reeves, best known for directing the horror-thrill ride movie "Cloverfield," has taken over directing duties for the second movie in the "Planet of the Apes" rebooted franchise, "Dawn of the Planet of the Apes." The new movie, opening Friday, July 11, is set 10 years after a lethal plague has wiped out most of the human race and led to an ape-dominated world.
8. Summertime horror flick
Feel like celebrating the Fourth of July with a scare-your-socks-off horror movie about demonic possession? "Deliver Us From Evil," starring Eric Bana and Olivia Munn, is based on a book co-written by New York policeman Ralph Sarchie about his encounters with the paranormal. In theaters Wednesday, July 2.
9. Arts festival in Mentor
The Wildwood Fine Arts Festival features more than 60 arts and crafts booth spread out around the historic Manor House at Wildwood Cultural Center in Mentor. This one-day event runs 10:30 a.m. to 5 p.m. Sunday, June 29. $2. 7645 Little Mountain Road, Mentor.
10. Fantasy TV show premieres
"The Leftovers" is a new fantasy-drama television show co-written and co-produced by Damon Lindelof, one of the masterminds behind "Lost." His new show doesn't have islands, hatches or smoke monsters, but it is moody, ambitious and mysterious. "The Leftovers" picks up three years after what's called the Sudden Departure made 140 million people vanish and left the survivors to cope with a new world. Premieres at 10 p.m. Sunday, June 29 on HBO.


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The Special Education Teacher is responsible for planning, structuring, implementing and evaluating the behavioral and educational components of their classroom. This position oversees the daily operations of their classroom and assumes responsibility for the design and implementation of IEP goals and objectives. This position supervises and offers guidance to classroom staff to ensure a positive and high quality teaching environment, and ensures compliance with agency policies and procedures and other appropriate regulations and standards.
- Minimum Requirements:
Must hold a valid CA Special Education Teaching Credential, Intern Credential or Substitute Credential.* At least two years of experience working with developmentally disabled and / or emotionally disturbed students in an environment utilizing an Applied Behavior Analysis approach.
- Must have computer access with internet capabilities.
Supervisory experience is highly (preferred).
Click the link below for a list of our current openings: http://www.anovaeducation.org/page.cfm?p=516
How to apply
If you meet these requirements and are ready to move into a rewarding and challenging new career, we'd love to hear from you! Please send a cover letter including salary requirements and resume to:firstname.lastname@example.com.
150 Lovell Avenue, San Rafael, CA, 95403, US


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As, I'm sure you're all aware B-17G (N390TH) crashed last summer. Fortunately no one was hurt, but the aircraft was a total loss... or was it?
The Liberty Belle's website now says it will be rebuilt! They do not have any other information that I can find, and based on the photos I saw of the wreck I find this incredibly hard to believe. So, does anyone else know more?
Below is a link to the liberty foundation's website where you will see under the "Important points to know" section right on the front page the claim that the plane will be rebuilt.


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Royal St. Charles Hotel, 135 St. Charles Ave., 504.587.1330
This semicircular nightspot blends a cool Asian aesthetic with a laid-back, late-night vibe. Floor-to-ceiling windows face Common Street, giving the club a fishbowl feel. DJs keep the down-tempo house music thumping into the wee hours, drawing the hipsters and the after-work hospitality industry crowd. Ohm has an attitude like its name, relaxed yet focused.
Try: "Wine Down Wednesdays" free wine and sake tastings and complimentary hors d'oeuvres from 5 to 8 p.m. Happy hour Mondays through Thursdays, 5 to 8 p.m..


text: I have a different problem with the same device (N670 Plus to be exact): when I replaced the original iGO version with another one that had full Europe map & generic license. After restarting, I did have access to all maps and could earch and find locations, POIs etc on them, but the GPS receiver was deactivated and I couldn't reactivate it. Is this something common? What should I do about it?


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Floyd E. Hunter, who shot and killed his son, Christopher, then himself Sunday morning, believed his health was deteriorating, Cayuga County sheriff's investigators said today.
Sheriff David S. Gould said Hunter talked about his health in a note found in his Turner Road home in Cato. Gould would not release the content of the note, except to say that in it Hunter wrote that he believed he was getting sicker.
The sheriff would not confirm a report from a neighbor that Floyd Hunter had Huntington's disease, a genetically programmed degeneration of brain cells that causes uncontrolled movements, loss of intellectual faculties and emotional disturbance.
The sheriff said Hunter's note showed that the killings -- ruled a murder-suicide -- were planned in advance and were not done on the spur of the moment.
Gould said an autopsy showed that Christopher Hunter, 18, was killed several hours before Floyd Hunter killed himself. Each died from a single gunshot to the head.


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HOLLAND, MI -- The West Michigan boxing presence is starting to grow for the MotorCity Casino's Night of Knockouts III in Detroit Thursday, March 7.
Hudsonville native Jordan Shimmell (8-0, 7 KOs) announced late last year that he'd be competing in the event and is still waiting to finalize a challenger, but another boxer from the area has his plans all set.
Holland's Thomas Amaro (2-0) has announced he'll be on the fight card in a six-round bout versus Tony Harrison (11-0, 8 KOs).
Amaro was last in action at the Orbit Room on Jan. 12 where he defeated Michael Pickett.
RELATED: Holland boxer Johnny Garcia to train at Wild Card Gym in California
"It's a six-rounder this time instead of four," Amaro said. "I feel comfortable but it's going to be a little awkward because I'm not used to going six rounds. He's going to be a hard fighter so I'm sure it will be a challenge."
Amaro got back into the fight game after taking years off at the urge of his students at Venture Boxing in Holland. They wanted to see him fight.
"I'm a little nervous. but I've been through it since I was young," Amaro said. "With my experience, since I'm 36 years old and he's (22), I think I have a good chance but I'm just going to give it all I've got."
Amaro said he knows he's going up against his toughest opponent yet.
"One of us is going to walk out with a first loss, and I'm hoping it's going to be him," Amaro said. "The way they've got me training right now I'm pretty sure I'll be (winning) this fight."
Follow Cory Olsen on Twitter or email him at email@example.com


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This week, the Hanover-Horton School Board agreed to lend a hand to home sellers and buyers in the area. The school district will include a link on its website to homes that are on the market. One real estate agent said 82 homes are for sale in the district today.
The early onset of warm weather might provide a kick-start to the homebuying season, and perhaps not a moment too soon. Real estate values in Jackson County have tumbled in the last few years, as they have in Michigan and throughout the U.S.
With the economy improving, do you believe that trend will turn the other way? Will home values in Jackson County climb this year? Tell us why, whether it's based on "For Sale" signs in your neighborhood or other evidence.
We particularly want to hear from folks who are looking to buy homes or who are selling. If you are a real estate agent, bring your expertise to the table.


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Product Tags: Bloody Mary,


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The Bee is reporting Les Schwab has purchased the property that currently houses Kasch's Nursery. Les Schwab currently has two locations within a few miles, one on Powell and another farther south on McLoughlin. While Les Schwab is seemingly loved by all and a favorite subject of business professors accross the country, the addition of a tire center will likely benefit those passing by, rather than Sellwood residents, who tend to favor two wheels or two feet a bit more than your average neighborhood.
Kasch's will be missed, but Les Schwab is sure to be a good neighbor, even if the contribution to the neighborhood appears minimal.


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Gov. Robert Bentley announced grants for 34 road and bridge projects in the second phase of the first round of the Alabama Transportation Rehabilitation and Improvement Program, or ATRIP for short.
The Tuscaloosa County projects are a $1.25 million bridge on South Sandy Road over Big Sandy Creek, a $400,000 bridge on Moccasin Branch Road over an unnamed tributary and a $400,000 bridge improvement project on Dobbs Road over Thornton Creek.
"With these additional projects, we are moving closer to our goal of improving the safety of roads and bridges throughout Alabama," Bentley said in a news release. "Many of our bridges are in desperate need of repair or replacement. Many of our roads are outdated and cannot handle current demand. Through ATRIP, we are able to make needed improvements to enhance public safety and quality of life in our communities."
In May, the state announced that ATRIP would provide funds for the
$675,000 resurfacing of Crescent Ridge Road and the $1,623,626 third phase of Loop Road improvements from Fairmont Drive to Woodland Road.
Eighty percent of ATRIP funding is covered by federal Grant Anticipation Revenue Vehicle, or GARVEE, bonds and 20 percent of the cost must be provided by local governments or public-private partnerships.


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I agree, Apresher. It will also be interesting to see how medical professionals accept this tool. Will they see it as a helpful diagnostic tool or will they see it as a threat.
You have a good point on item number 3, SparkyWatt. The acceptance of Watson by medical professionals may end up having a generational component. Those introduced to collaborating with a computer during school will probably feel they are in command of the collaboration.


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The Board of Directors of the Darwin R. Barker Library Association announces the appointment of Sara Hart as the Library's new Director. She replaces Joy Harper who retired April 1 after 26 years with the library. Mrs. Hart, a Chautauqua County native, earned a BA in Art History from SUNY at Fredonia and a Master of Library Science from the University at Buffalo. She also holds a New York State Public Librarian Certificate.
Article Photos
Sara Hart


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An Auburn football legend is returning to coach the Tigers on Gene Chizik's new staff.
Rocker was an All-American, SEC Player of the Year and winner of the Outland Trophy and the Lombardi Award for his play in the Auburn defensive line in the 1980s. He was inducted into the College Football Hall of Fame in 2004.
Rocker is leaving his job as the defensive line coach at Ole Miss after one season. He was Arkansas' defensive line coach the five years before that. Chizik has hired seven assistants, and needs two more to fill out his staff.
Rocker's other coaching stops include Cincinnati and before that he was at Troy.
Thompson, who was Florida's defensive coordinator in 2002, South Carolina's co-defensive coordinator in 2005 and Mississippi's defensive coordinator in 2007, has also coached at Alabama. He's been in the business for 25 years and is currently on Bill Curry's staff at Georgia State, a team that has yet to field a team.
Thompson was the head coach at East Carolina in 2003-04, and has also worked at Memphis, Southern Miss, Louisiana Tech and Northwestern State. He was also the athletics director at Central Arkansas, his alma mater, for a year.
Curry praised Thompson on the Georgia State website:
"John was with us at Alabama as a very young coach but an outstanding one, and we have stayed in touch through the years," said Curry. "He has coached at all those places because people have sought him out to be their defensive coordinator after they couldn't move the ball on him. He finds a way to convey a defensive that is simple to our players but utterly confusing to the opposing offense.''
Here's more from the Thompson's bio on the Georgia State web site:
Thompson was the defensive coordinator at Florida in 2002, when the Gators' pass defense was ranked seventh in the nation, allowing just 162.4 yards per game. He also spent two years at Arkansas, serving as co-defensive coordinator in 2000 and then defensive coordinator in 2001. In 2000, the Razorbacks were second in the nation in pass defense while leading the SEC in pass defense and total defense. The following year, Thompson helped lead Arkansas to the 2002 Cotton Bowl.
Thompson's first position as a defensive coordinator came at Northwestern State, where he served from 1983-86, and again from 1988-89 after spending the 1987 season at Alabama.


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For some reason, when I put mp3s files on my SD card, a duplicate file shows up that cannot be played.
Like, if I put "The Pretender" by Foo Fighters on it, a second track is right beneath it that says the same info but it cannot be played. This really messes up using the shuffle function.
Does anyone know the reason for this?
"Kids, let me tell you about another so-called "wicked" guy. He had long hair and some wild ideas, and he didn't always do what other people thought was right. And that man's name was... I forget. But the point is... well, I forget that too. Marge, you know who I'm talking about. He used to drive that blue car?"


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Results tagged ' 2013 WBC '
Rattler Alumni in World Baseball Classic – Stats Through (3/17)
Go here to see how everyone in the WBC were doing through last Sunday.
There are no updates to Australia, Canada, Taiwan, or Venezuela since those teams were done playing after last Sunday.
That left former Timber Rattlers players on USA, Italy, the Netherlands, and Puerto Rico still playing last week.
Puerto Rico is through to the Finals after a win over Japan on Sunday. The Netherlands will play the Dominican Republic tonight to see who will face Puerto Rico for the 2013 WBC Championship on Tuesday night.
Adam Jones: 6g, 4-for-22 (.182), 0HR, 4RBI
Jonathan Lucroy: 3g, 2-for-5 (.400), 0HR, 1RBI
An RBI single by Jones in the game against Puerto Rico:
Alex Liddi: 5g, 4-for-17 (.235); 0HR, 3RBI:
From early in the WBC, an Alex Liddi RBI single:
The Netherlands:
Wladimir Balentien: 6g, 6-for-19 (.316), 0HR, 4RBI
Kalian Sams: 6g, 5-for-19 (.263), 7 RUNS, 0HR, 3RBI
Here's a Balentien RBI single in a game against Korea from earlier in the tournament:
Puerto Rico:
Martin Maldonado: 5g, 0-for-9 (.000), 0HR, 0RBI
Hiram Burgos: 2g, 0gs, 1-0, 0.00ERA, 8.1IP, 3BB, 7K
Shared this on twitter, but here are some scoreless frames from Burgos – including a strikeout of Liddi – in Puerto Rico's win over Italy:
This is a test of the Video Embedding Service
I was told that I could embed MLB video last year. I am getting around to testing it out today. If it works, expect this to be a frequent topic during the season.
Okay, the Khris Davis RBI single from Monday's game against the Dodgers could not be embedded yet. So, here is an MLB video from March 7 with quotes from Davis ('10) and Ron Roenicke on his productive camp:
This video from MLB is about the opportunities for Scooter Gennett ('10) and Hunter Morris ('10) in Big League Camp during Spring Training.
How about a few highlights from the WBC?
Kalian Sams ('07) with a walkoff sacrifice fly for the Dutch to beat the Cubans.
Adam Jones ('04) with his 2-run double off Jim Henderson ('09) to put the US in front of Canada:
Michael Saunders ('06) with a 2-run homer for Canada:
Michael Saunders winning the Pool D MVP
Rattler Alumni in World Baseball Classic – Stats Edition
Yes. That was former Timber Rattlers outfielder Kalian Sams with the game winning sacrifice fly for the Netherlands today. The Dutch beat Cuba 7-6 in Tokyo to advance to the next round of the World Baseball Classic.
Here is a look at how the ex-Rattlers have done during the WBC.
Adam Jones: 2-for-9, 3RBI
Jonathan Lucroy: 2-for-5, RBI
Chris Snelling: 1-for-2
Mike Walker: 5-for-11
Ryan Rowland-Smith: 2g, 1.2IP, 2H, R, BB, K
Taylor Green: 4-for-14
Michael Saunders: 8-for-11, 4 RUNS, HR, 7RBI*
Phillippe Aumont: 2g, 1.2IP, 5H, 3R, BB, K
Jim Henderson: 2g, 0-1, IP, 5H, 5R, BB, K
Yung Chi-Chen: 4-for-19, RBI
Alex Liddi: 4-for-10, 2RBI
Wladimir Balentien: 5-for-18, 4RBI
Kalian Sams: 3-for-13, RBI
Puerto Rico:
Martin Maldonado: 0-for-5
Hiram Burgos: 1g, 4.2IP, 0R, BB, 3K
Asdrubal Cabrera: 1-for-8
Cesar Jimenez: 2g, 1.1IP, 3H, 2R, 0BB, K
Rowland-Smith & Snelling for Australia
Big League Stew had a post over the weekend about the Australian team for the World Baseball Classic.
It was titled: Getting to know your World Baseball Classic Squads: Australia
Kevin Kaduk gets to names that Timber Rattlers fans should know well.
Biggest star(s): Though he hasn't pitched in the majors since 2010, Ryan Rowland-Smith is a familiar name to many baseball fans. Infielder Luke Hughes has also played for a couple of big league teams, most recently Oakland.
Name you may not know, but should: Remember Chris Snelling? Once a decently-rated prospect in the early 2000s, the outfielder experienced a string of injuries and only played 93 big league games. Now 31, Snelling will try and help the Aussies grab some WBC glory.
RRS struggled with the Rattlers in 2002 and was sent down to Everett. RRS pitched great in 2003 and was sent up to the California League before the All-Star Break.
Snelling is 31 now? *sigh*
He had a great season in 2000, but he was injured for a lot of it. I want him to stay healthy and play well in the WBC. Then, I want to see someone sign him to get another shot.
Later in the post Kaduk explains why Travis Blackley is not pitching for Australia this year.
I bring up Blackley because he is one of those guys who probably SHOULD have been a member of the Timber Rattlers in 2002. He was 19 and had only pitched in Everett (Northwest League). The Mariners sent him to San Bernadino to start that season where he had a walk to strikeout ratio of 44:152 in 121-1/3 innings. Sure would have been nice to have to have Blackley in Appleton for at least the first half of that '02 season.
I'm not bitter.
Guide to Rattlers Alumni in 2013 World Baseball Classic
The rosters are out for the 2013 World Baseball Classic. There are
23 19 20 players who have suited up as Timber Rattlers on 12 9 of the 28 16 teams. (*See update at the bottom of the post).
Let's take a look:
Adam Jones (2004)
Jonathan Lucroy (2012)
Australia (
2 3):
Ryan Rowland-Smith (2002, 2003)
Chris Snelling (2000)
Mike Walker??? yes Mike Walker (2011)
Canada (5):
Phillippe Aumont (2008)
Taylor Green (2009)
Jim Henderson (2009)
Brett Lawrie (2009)
Michael Saunders (2006)
Colombia (1):
Marwin Vega (2006)
Dominican Republic (1):
Carlos Gomez (2010, 2011, 2012)
Israel (1):
Brett Lorin (2008)
Alex Liddi (2006, 2007, 2008)
Nicaragua (2):
Ron Garth (2006, 2007, 2008)
J.C. Ramirez (2008)
Netherlands (2):
Wladimir Balentien (2004)
Kalian Sams (2007)
Puerto Rico:
Hiram Bugos (2010)
Martin Maldonado (2009)
Yung-Chi Chen (2005)
Venezuela (3):
Asdrubal Cabrera (2005)
Felix Hernandez (2003)
Cesar Jimenez (2003)
*-Alert reader Kyle from Brew Crew Ball points out that Israel, Nicaragua, & Colombia did not make the field of 16 for the 2013 WBC. But, as I pointed out in the comments. I had those pictures and I was going to use those pictures. Plus, as I did not point out in the comments, any time I can mention Marwin Vega…I am going to mention Marwin Vega.
UPDATE TWO: The Australian Baseball Digest was confused by the addition of Mike Walker to Australia, too. His mother is Australian. That makes him eligible for Team Australia.


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Today's discussion lasted almost 90 minutes, with nearly triple the usual traffic. Must be football season and Michigan week.
Tons of topics covered. Most questions answered.
From predictions, to the women on U-M's campus to how many WMU players would start at Michigan (Carder over Robinson?). It's all here.
Click below for the replay.


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This deal has ended.
For a limited time, get this Simmons Kids Slumber Time Naturally Mattress, $109.99, for free in your cart at checkout when you purchase select Simmons Cribs at Target (eligible cribs are marked "Free mattress with purchase.") This Simmons Kids Slumbertime Augustana 4-in-1 Convertible Crib, normally $349.99 and on sale for $299, gets you the mattress. There is a $40 handling fee. The best shipped price we found on this crib without the mattress anywhere else was $379. It can be used as a crib, a toddler bed, aday and to full size bed with headboard & footboard, although guard rails and conversion rails are sold separately. It is wood with a 90 day manufacturer's warranty. The mattress is 6" thick and has a limited lifetime manufacturer's warranty. Sales tax is charged in most states.No longer available


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CULVER CITY, Calif. -- Another "event" sell-through video title originally thought to be pencilled in for the early part of next year has been announced for this fourth quarter. "Matilda," a family-oriented title starring Danny DeVito and Rhea Perlman, will be released direct to the sell-through market Dec. 17 by Columbia TriStar Home Video here. The title has a minimum advertised price of $15.95, but no suggested retail price, an unusual but not unprecedented strategy. The pay-per-view ...
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