ROC curve regression analysis: the use of ordinal regression models for diagnostic test assessment.

Diagnostic tests commonly are characterized by their true positive (sensitivity) and true negative (specificity) classification rates, which rely on a single decision threshold to classify a test result as positive. A more complete description of test accuracy is given by the receiver operating characteristic (ROC) curve, a graph of the false positive and true positive rates obtained as the decision threshold is varied. A generalized regression methodology, which uses a class of ordinal regression models to estimate smoothed ROC curves has been described. Data from a multi-institutional study comparing the accuracy of magnetic resonance (MR) imaging with computed tomography (CT) in detecting liver metastases, which are ideally suited for ROC regression analysis, are described. The general regression model is introduced and an estimate for the area under the ROC curve and its standard error using parameters of the ordinal regression model is given. An analysis of the liver data that highlights the utility of the methodology in parsimoniously adjusting comparisons for covariates is presented

Effect of Aging on the Reversibility of Pu(IV) Sorption to Goethite

Designing safe remediation and disposal strategies for plutonium (Pu) requires understanding the sorption affinity of Pu for soil minerals. Sorption of Pu(IV) was examined with respect to aging for a goethite system using batch sorption experiments. Sorption of Pu(IV) to iron oxides has been observed to be strong, rapid, and possibly irreversible or hysteretic. These observations may be explained by aging, a surface chemical process happening after initial sorption which causes a change in contaminant surface speciation over time. Measurements of Pu(IV) sorption are often complicated by oxidative leaching of Pu(IV) as Pu(V). Desferrioxamine B (DFOB) is a complexant capable of competing with the proposed strong surface complexes. Additionally, DFOB minimizes oxidative leaching by forming strong Pu(IV)-DFOB complexes, thereby stabilizing Pu(IV) as the dominant aqueous oxidation state. Pu(IV) was reacted in suspensions of 0.1g/L goethite and 10mM NaCl spanning pH 4–7 for various lengths of time (1,6,15,34 and 116 days). Supernatant was replaced with a 1.7µM DFOB solution and, after 34 more days, analyzed for aqueous Pu by liquid scintillation counting. Modeling sorption curves in FITEQL yielded logK values which increased from 0.078 to 0.953 over 116 days, indicating Pu(IV) sorption onto goethite becomes less reversible with aging

Antigenicity of Recombinant Maltose Binding Protein-Mycobacterium avium subsp. paratuberculosis Fusion Proteins with and without Factor Xa Cleaving

Mycobacterium avium subsp. paratuberculosis causes Johne’s disease (JD) in ruminants. Proteomic studies have shown that M. avium subsp. paratuberculosis expresses certain proteins when exposed to in vitro physiological stress conditions similar to the conditions experienced within a host during natural infection. Such proteins are hypothesized to be ex- pressed in vivo, are recognized by the host immune system, and may be of potential use in the diagnosis of JD. In this study, 50 recombinant maltose binding protein (MBP)-M. avium subsp. paratuberculosis fusion proteins were evaluated using serum samples from sheep infected with M. avium subsp. paratuberculosis, and 29 (58%) were found to be antigenic. Among 50 fusion proteins, 10 were evaluated in MBP fusion and factor Xa-cleaved forms. A total of 31 proteins (62%) were found to be antigenic in either MBP fusion or factor Xa-cleaved forms. Antigenicity after cleavage and removal of the MBP tag was marginally enhanced

Antigenicity of Recombinant Maltose Binding Protein-Mycobacterium avium subsp. paratuberculosis Fusion Proteins with and without Factor Xa Cleaving

Mycobacterium avium subsp. paratuberculosis causes Johne’s disease (JD) in ruminants. Proteomic studies have shown that M. avium subsp. paratuberculosis expresses certain proteins when exposed to in vitro physiological stress conditions similar to the conditions experienced within a host during natural infection. Such proteins are hypothesized to be ex- pressed in vivo, are recognized by the host immune system, and may be of potential use in the diagnosis of JD. In this study, 50 recombinant maltose binding protein (MBP)-M. avium subsp. paratuberculosis fusion proteins were evaluated using serum samples from sheep infected with M. avium subsp. paratuberculosis, and 29 (58%) were found to be antigenic. Among 50 fusion proteins, 10 were evaluated in MBP fusion and factor Xa-cleaved forms. A total of 31 proteins (62%) were found to be antigenic in either MBP fusion or factor Xa-cleaved forms. Antigenicity after cleavage and removal of the MBP tag was marginally enhanced

Use of thymidine analogues to indicate vascular perfusion in tumours

Temporary reduction in blood-flow within tumour blood vessels can reduce oxygen supply leading to transient perfusion-limited hypoxia. Consequent selection of cells with mutations and reduced radiosensitivity can lead to disease progression and treatment-resistance. In the present study, we investigated whether heterogeneity of labelling after thymidine analogue administration is related to perfusion variations, and if so, could it be quantified and used as a perfusion indicator. Perfusion in murine RIF1 tumours was reduced by hydralazine or increased by nicotinamide and the mice subsequently injected with IdUrd. Tumours were halved for analysis by both flow cytometry and immunohistochemistry. Tumour sections were stained for vasculature and IdUrd. Each blood vessel was scored for the density of IdUrd-labelled cells surrounding it, using a semi-quantitative scoring system. Flow cytometry showed that the IdUrd labelling index and intensity decreased by approximately 50% after hydralazine. In tumour sections of control animals, 2.9% of vessels showed no IdUrd label. In contrast, after hydralazine almost 50% of vessels had no surrounding IdUrd labelling, whereas after nicotinamide there were fewer vessels with low labelling and a higher median score. In conclusion, changes of tumour perfusion by pharmacological agents is reflected in changes in tumour-cell labelling by the thymidine analogue IdUrd, suggesting that IdUrd labelling could be used to indicate perfusion in individual vessels in human tumours. © 2000 Cancer Research Campaig

Plutonium stabilization in zircon: Effects of self-radiation

Zircon (ZrSiO4)(ZrSiO4) is the most thoroughly studied of all candidate ceramic phases for the stabilization of plutonium. Self-radiation damage from α-decay of the 239Pu,239Pu, which releases a 5.16 MeV α-particle and a 0.086 MeV 235U235U recoil nucleus, can significantly affect the structure and properties of zircon. Recent computer simulations using energy minimization techniques indicate that the lowest energy configuration occurs for a defect cluster composed of two near-neighbor Pu3+Pu3+ substitutions on Zr4+Zr4+ sites and a neighboring charge-compensating oxygen vacancy. © 2000 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87571/2/18_1.pd

Linking Physical Education With Community Sport and Recreation: A Program for Adolescent Girls

The engagement of adolescent girls in physical activity (PA) is a persistent challenge. School-based PA programs have often met with little success because of the lack of linkages between school and community PA settings. The Triple G program aimed to improve PA levels of secondary school girls (12-15 years) in regional Victoria, Australia. The program included a school-based physical education (PE) component that uniquely incorporated student-centered teaching and behavioral skill development. The school component was conceptually and practically linked to a community component that emphasized appropriate structures for participation. The program was informed by ethnographic fieldwork to understand the contextual factors that affect girls’ participation in PA. A collaborative intervention design was undertaken to align with PE curriculum and coaching and instructional approaches in community PA settings. The theoretical framework for the intervention was the socioecological model that was underpinned by both individual-level (social cognitive theory) and organizational-level (building organizational/community capacity) strategies. The program model provides an innovative conceptual framework for linking school PE with community sport and recreation and may benefit other PA programs seeking to engage adolescent girls. The objective of this article is to describe program development and the unique theoretical framework and curriculum approaches

Examining the common aetiology of serous ovarian cancers and basal-like breast cancers using double primaries

Background: The somatic molecular profiles of basal-like breast cancers and high-grade serous ovarian cancers share many similarities, leading to the hypothesis that they have similar aetiologies, in which case they should occur together in the same patient more often than expected. Methods: We identified 545 women with double independent primary cancers of the breast and ovary reported to the California Cancer Registry from 1999 to 2013 and examined the coincidence of subtype combinations. Results: For most subtype combinations the observed frequencies were similar to their expected frequencies, but in 103 observed cases vs 43.8 expected (O/E=2.35; 95% CI 1.90–2.81) a triple-negative breast tumour (typically basal-like) was matched with a serous ovarian tumour (typically high-grade). Conclusions: The results provide compelling evidence that basal-like breast cancer and high-grade serous ovarian cancer share a much more similar aetiology than breast and ovarian cancers more broadly. Further research is needed to clarify the influence of germ-line BRCA1 mutations and other risk factors on these results

Near-Edge X-ray Absorption Fine Structure Study of Ion-beam-induced Phase Transformation in Gd2(Ti1-yZry)2O7

The structural and electronic properties of Gd2(Ti1−yZry)2O7 (y=0–1) pyrochlores following a 2.0-MeV Au2+ ion-beam irradiation (~5.0 X 1014 Au2+/cm2) have been investigated by Ti 2p and O 1s near-edge x-ray absorption fine structure (NEXAFS). The irradiation of Gd2(Ti1−yZry)2O7 leads to the phase transformation from the ordered pyrochlore structure (Fd3m) to the defect fluorite structure (Fm3m) regardless of Zr concentration. Irradiated Gd2(Ti1−yZry)2O7 with y≤0.5 are amorphous, although significant short-range order is present. Contrasting to this behavior, compositions with y≥0.75 retain crystallinity in the defect fluorite structure following irradiation. The local structures of Zr4+ in the irradiated Gd2(Ti1−yZry)2O7 with y≥0.75 determined by NEXAFS are the same as in the cubic fluorite-structured yttria-stabilized zirconia (Y–ZrO2), thereby providing conclusive evidence for the phase transformation. The TiO6 octahedra present in Gd2(Ti1−yZry)2O7 are completely modified by ion-beam irradiation to TiOx polyhedra, and the Ti coordination is increased to eight with longer Ti–O bond distances. The similarity between cation sites and the degree of disorder in Gd2Zr2O7 facilitate the rearrangement and relaxation of Gd, Zr, and O ions/defects. This inhibits amorphization during the ion-beam-induced phase transition to the radiation-resistant defect fluorite structure, which is in contrast to the ordered Gd2Ti2O7