Combining Existing Monitoring Sites with a Probability Survey Design-Examples from U.S. EPA’s National Coastal Assessment

U.S. Environmental Protection Agency’s (EPA’s) National Coastal Assessment was envisioned as a research effort led by EPA’s Office of Research and Development to evaluate assessment methods for ecosystem condition monitoring. The program was conducted through strategic partnerships with the coastal states. These states conducted the survey in their waters with a common set of indicators. The resources targeted for initial monitoring were estuarine waters. A flexible probability survey design was used to incorporate, to the extent possible, existing state monitoring program sites. Three criteria were developed to evaluate existing monitoring program sites in the northeastern United States for possible incorporation into the national design: (1) the sites were selected to be representative, (2) the variables sampled at the sites were similar in distribution with variables from a probability design, and (3) the correlation structure of variables was equivalent to that for a probability design. Detailed examples were presented for Long Island Sound water quality sites, New Jersey coastal water quality sites, and Casco Bay, ME, sediment sites to illustrate the approach

Impurity spin relaxation in S=1/2 XX chains

Dynamic autocorrelations $$ (\alpha=x,z) of an isolated impurity spin in a S=1/2 XX chain are calculated. The impurity spin, defined by a local change in the nearest-neighbor coupling, is either in the bulk or at the boundary of the open-ended chain. The exact numerical calculation of the correlations employs the Jordan-Wigner mapping from spin operators to Fermi operators; effects of finite system size can be eliminated. Two distinct temperature regimes are observed in the long-time asymptotic behavior. At T=0 only power laws are present. At high T the x correlation decays exponentially (except at short times) while the z correlation still shows an asymptotic power law (different from the one at T=0) after an intermediate exponential phase. The boundary impurity correlations follow power laws at all T. The power laws for the z correlation and the boundary correlations can be deduced from the impurity-induced changes in the properties of the Jordan-Wigner fermion states.Comment: Final version to be published in Phys. Rev. B. Three references added, extended discussion of relation to previous wor

Theiler's Murine Encephalomyelitis Virus as a Vaccine Candidate for Immunotherapy

The induction of sterilizing T-cell responses to tumors is a major goal in the development of T-cell vaccines for treating cancer. Although specific components of anti-viral CD8+ immunity are well characterized, we still lack the ability to mimic viral CD8+ T-cell responses in therapeutic settings for treating cancers. Infection with the picornavirus Theiler's murine encephalomyelitis virus (TMEV) induces a strong sterilizing CD8+ T-cell response. In the absence of sterilizing immunity, the virus causes a persistent infection. We capitalized on the ability of TMEV to induce strong cellular immunity even under conditions of immune deficiency by modifying the virus to evaluate its potential as a T-cell vaccine. The introduction of defined CD8+ T-cell epitopes into the leader sequence of the TMEV genome generates an attenuated vaccine strain that can efficiently drive CD8+ T-cell responses to the targeted antigen. This virus activates T-cells in a manner that is capable of inducing targeted tissue damage and glucose dysregulation in an adoptive T-cell transfer model of diabetes mellitus. As a therapeutic vaccine for the treatment of established melanoma, epitope-modified TMEV can induce strong cytotoxic T-cell responses and promote infiltration of the T-cells into established tumors, ultimately leading to a delay in tumor growth and improved survival of vaccinated animals. We propose that epitope-modified TMEV is an excellent candidate for further development as a human T-cell vaccine for use in immunotherapy

Performance of Survivin mRNA as a Biomarker for Bladder Cancer in the Prospective Study UroScreen

BACKGROUND: Urinary biomarkers have the potential to improve the early detection of bladder cancer. Most of the various known markers, however, have only been evaluated in studies with cross-sectional design. For proper validation a longitudinal design would be preferable. We used the prospective study UroScreen to evaluate survivin, a potential biomarker that has multiple functions in carcinogenesis. METHODS/RESULTS: Survivin was analyzed in 5,716 urine samples from 1,540 chemical workers previously exposed to aromatic amines. The workers participated in a surveillance program with yearly examinations between 2003 and 2010. RNA was extracted from urinary cells and survivin was determined by Real-Time PCR. During the study, 19 bladder tumors were detected. Multivariate generalized estimation equation (GEE) models showed that β-actin, representing RNA yield and quality, had the strongest influence on survivin positivity. Inflammation, hematuria and smoking did not confound the results. Survivin had a sensitivity of 21.1% for all and 36.4% for high-grade tumors. Specificity was 97.5%, the positive predictive value (PPV) 9.5%, and the negative predictive value (NPV) 99.0%. CONCLUSIONS: In this prospective and so far largest study on survivin, the marker showed a good NPV and specificity but a low PPV and sensitivity. This was partly due to the low number of cases, which limits the validity of the results. Compliance, urine quality, problems with the assay, and mRNA stability influenced the performance of survivin. However, most issues could be addressed with a more reliable assay in the future. One important finding is that survivin was not influenced by confounders like inflammation and exhibited a relatively low number of false-positives. Therefore, despite the low sensitivity, survivin may still be considered as a component of a multimarker panel