Veeresh Gadag

Aptima HPV E6/E7 mRNA Test Is as Sensitive as Hybrid Capture 2 Assay but More Specific at Detecting Cervical Precancer and Cancer

ABSTRACT Detection of human papillomavirus (HPV) E6/E7 oncogene expression may be more predictive of cervical cancer risk than testing for HPV DNA. The Aptima HPV test (Gen-Probe) detects E6/E7 mRNA of 14 oncogenic types. Its clinical performance was compared with that of the Hybrid Capture 2 DNA test (HC2; Qiagen) in women referred for colposcopy and those routinely screened. Aptima was also compared with the PreTect HPV-Proofer E6/E7 mRNA assay (Proofer; Norchip) in the referral population. Cervical specimens collected in PreservCyt (Hologic Inc.) were processed for HPV detection and genotyping with the Linear Array (LA) method (Roche Molecular Diagnostics, Laval, Quebec, Canada). Histology-confirmed high-grade cervical intraepithelial neoplasia (CIN 2) or worse (CIN 2+) served as the disease endpoint. On the basis of 1,418 referral cases (CIN 2+, n = 401), the sensitivity of Aptima was 96.3% (95% confidence interval [CI], 94.4, 98.2), whereas it was 94.3% (95% CI, 92.0, 96.6) for HC2. The specificities were 43.2% (95% CI, 40.2, 46.2) and 38.7% (95% CI, 35.7, 41.7), respectively (P < 0.05). In 1,373 women undergoing routine screening (CIN 2+, n = 7), both Aptima and HC2 showed 100% sensitivity, and the specificities were 88.3% (95% CI, 86.6, 90.0) and 85.3% (95% CI, 83.5, 87.3), respectively (P < 0.05); for women ≥30 years of age (n = 845), the specificities were 93.9% (95% CI, 92.3, 95.5) and 92.1% (95% CI, 90.3, 93.9), respectively (P < 0.05). On the basis of 818 referral cases (CIN 2+, n = 235), the sensitivity of Aptima was 94.9% (95% CI, 92.1, 97.7) and that of Proofer was 79.1% (95% CI, 73.9, 84.3), and the specificities were 45.8% (95% CI, 41.8, 49.8) and 75.1% (95% CI, 71.6, 78.6), respectively (P < 0.05). Both Aptima and Proofer showed a higher degree of agreement with LA genotyping than HC2. In conclusion, the Aptima test is as sensitive as HC2 but more specific for detecting CIN 2+ and can serve as a reliable test for both primary cervical cancer screening and the triage of borderline cytological abnormalities.

Clinical Performance of the PreTect HPV-Proofer E6/E7 mRNA Assay in Comparison with That of the Hybrid Capture 2 Test for Identification of Women at Risk of Cervical Cancer

ABSTRACT Human papillomavirus (HPV) DNA testing has a higher clinical sensitivity than cytology for the detection of high-grade cervical intraepithelial neoplasia or worse (CIN 2+). However, an improvement in specificity would be desirable. As malignant transformation is induced by HPV E6/E7 oncogenes, detection of E6/E7 oncogene activity may improve specificity and be more predictive of cervical cancer risk. The PreTect HPV-Proofer assay (Proofer; Norchip) detects E6/E7 mRNA transcripts from HPV types 16, 18, 31, 33, and 45 with simultaneous genotype-specific identification. The clinical performance of this assay was assessed in a cross-sectional study of women referred for colposcopy in comparison with the Hybrid Capture 2 (HC2; Qiagen) test, which detects DNA of 13 high-risk oncogenic HPV types collectively. Cervical specimens were collected in PreservCyt, and cytology was performed using the ThinPrep method (Hologic). The samples were processed for HPV detection with Proofer and HC2 and genotyping with the Linear Array method (Roche Molecular Systems). Histology-confirmed CIN 2+ served as the disease endpoint to assess the clinical performance of the tests. A total of 1,551 women were studied, and of these, 402 (25.9%) were diagnosed with CIN 2+ on histology. The Proofer assay showed a sensitivity of 78.1% (95% confidence interval [CI], 74.1 to 82.1) versus 95.8% (95% CI, 93.8 to 97.8) for HC2 (P < 0.05) and a specificity of 75.5% (95% CI, 73.0 to 78.0) versus 39.6% (95% CI, 36.8 to 42.4), respectively (P < 0.05). The lower sensitivity and higher specificity of Proofer for detection of CIN 2+ can be attributed to the fact that this test detects the expression of E6/E7 genes beyond a threshold from a limited number of oncogenic HPV types. In conclusion, Proofer is more specific than HC2 in identifying women with CIN 2+ but has a lower sensitivity.

Measles and rubella antibody response after measles-mumps-rubella vaccination in children with afebrile upper respiratory tract infection

The effect of concurrent afebrile viral upper respiratory tract infection (URI) on measles and rubella serum antibody response after measles-mumps-rubella (MMR) vaccination was determined in 580 1-year-old children, 369 with URI and 211 without URI, with the use of preimmunization and postimmunization sera. The presence of URI during the preceding 28 days, at the time of, or up to 7 days after immunization had no effect on the antibody response to either the measles or the rubella component of the vaccine. These findings support the recommendation that MMR vaccine be give to children at the recommended age regardless of the presence of afebrile viral URI.

Functional quantitative security risk analysis (QSRA) to assist in protecting critical process infrastructure

Abstract This article proposes a quantitative security risk assessment methodology that can assist management in the decision-making process where and when to protect critical assets of a chemical facility. An improvement upon previous work is the approach of conducting concurrent Threat and Vulnerability Assessments, as opposed to a sequential approach. Furthermore, this method introduces a Bow Tie risk model mapped into a Bayesian Network model that allows for various logical relaxation assumptions to be applied. Different uncertainty relaxation approaches such as “Noisy-OR” and “Leaky Noisy-OR” and “Noisy-AND” are tested to improve Threat and Vulnerability likelihood. Finally, integrating threat/vulnerability likelihood with potential losses, the security risk is quantified. The potential security countermeasures are characterized into either decreasing vulnerability or decreasing threat likelihood and are reassessed considering a cost analysis. A theoretical case study is conducted to exemplify the execution and application of the proposed method.

Fructose and moderately high dietary salt-induced hypertension: prevention by a combination of N-acetylcysteine and l-arginine

Diets containing 8% salt or 4% fructose (FR) cause insulin resistance and increase tissue methylglyoxal and advanced glycation end products (AGEs), platelet cytosolic-free calcium, and systolic blood pressure (SBP) in rats. In WKY rats, we have shown that moderately high salt, 4% NaCl (MHS) alone in diet does not cause hypertension, and when given along with 4% FR it does not have an additive effect. N-acetylcysteine (NAC) or l-arginine (ARG), treatment alone does not prevent hypertension in this model. The objectives of this study were to investigate the effect of NAC plus ARG in diet on SBP, platelet cytosolic-free calcium in a MHSxa0+xa0FR model, and to measure the plasma levels of methylglyoxal and the AGE, methylglyoxal-derived hydroimidazolone (MGH). At 7xa0weeks of age, WKY rats were divided into three groups: control group was given regular rat chow (0.7% NaCl) and water; MHSxa0+xa0FR group, diet containing 4% NaCl and 4% FR in drinking water; and MHSxa0+xa0FRxa0+xa0NACxa0+xa0ARG group, MHS diet supplemented with 1.5% N-acetylcysteine (NAC) and 1.5% l-arginine (ARG), and 4% FR in drinking water, and followed for 6xa0weeks. NACxa0+xa0ARG prevented the increase in platelet cytosolic-free calcium and SBP in MHSxa0+xa0FR treated rats. There was no difference in mean values of plasma methylglyoxal and MGH among the groups. In conclusion, NACxa0+xa0ARG treatment is effective in preventing hypertension in a moderately high saltxa0+xa0FR-induced animal model. Plasma methylglyoxal and MGH may not represent tissue modification or, alternatively, other tissue AGEs, derived from methylglyoxal or other aldehydes, may be involved in hypertension in this model.

Rubella antibody levels in school-aged children in Newfoundland: Implications for a two-dose rubella vaccination strategy

OBJECTIVEnTo determine the prevailing levels of rubella immunity among school-aged children who received a single dose of measles-mumps-rubella (MMR) vaccine at one year of age.nnnDESIGNnCross-sectional study with a two stage cluster sampling of randomly picked schools across the province of Newfoundland.nnnSTUDY POPULATION AND METHODSnA total of 1053, five to 17-year-old children were enrolled; vaccination history was verified through official records; and a sample of blood was taken. Rubella immunity was determined by enzyme immunoassay based on a serum antibody protective cut-off titre of more than 10 IU.nnnRESULTSnA total of 145 (13.8%) were found to be nonimmune. The rate of susceptibility ranged from 3.2% to 25.9% for different age groups. The proportion susceptible was significantly higher at 16.5% in the age group eight to 17 years old versus 3.9% for the age group five to eight years old (χ(2)=24.08; df=1, P<0.001). There was a significant regression of logarithm titre values on the age of children with an average decline in titre values of 8.1% per annum.nnnCONCLUSIONSnA substantial number of those who were given a single dose of MMR II vaccine may not have protective immunity against rubella as they reach prime reproductive age. There is a definite need to consider a two-dose rubella vaccination strategy in Canada, and these data suggest the second dose given after eight years of age will be most beneficial. In the move towards a routine two-dose measles vaccination strategy in Canada, the MMR II vaccine is being used for the second dose and given either at 18 months of age or at school entry. While this approach will have an overall beneficial effect, the impact of the above timing of the second dose on long term rubella immunity cannot be predicted at this time. These data also underscore the continuing need for prenatal rubella screening program.

Likelihood ratio tests for testing for multiple contaminants in the shocks and labelled slippage models

In the literature related to the study of lifelengths of experimental units, little attention has been paid to the models where shocks to the units generate outliers. In the present article, we consider a situation where n experimental units under investigation receive shocks at several time points. The parameter values of the lifelength distribution may change due to each shock, resulting in the generation of outliers. We derive the likelihood ratio test statistic to investigate if the shocks have significantly altered the parameter values. We also derive a likelihood ratio test under the labelled slippage alternative with multiple contaminations. Monte Carlo studies have been carried out to investigate the power of the proposed test statistics.