Hepatitis e Virus Genotype 3 Genomes from RNA-Positive but Serologically Negative Plasma Donors Have CUG as the Start Codon for ORF3

Hepatitis E virus (HEV) is a pathogen that causes hepatitis worldwide. Molecular studies have identified HEV RNA in blood products although its significance is not understood. This study was undertaken to characterize HEV genomes in asymptomatic plasma donors from Sweden and Germany lacking anti-HEV. Complete open reading frames (ORFs) were obtained from HEV strains in 5 out of 18 plasma donors who tested positive for HEV RNA. All strains had CUG as the start codon of ORF3, while 147 GenBank strains all had AUG as the start codon (p < 0.0001). This substitution was found in both interrelated and unrelated strains belonging to different phylogenetic clades. The HEV strains from the seronegative plasma donors had no other substitution in common, which may be why the CUG substitution seems to explain the seronegativity

Low-lying level structure of 56^{56}Cu and its implications on the rp process

The low-lying energy levels of proton-rich $^{56}$Cu have been extracted using in-beam $\gamma$-ray spectroscopy with the state-of-the-art $\gamma$-ray tracking array GRETINA in conjunction with the S800 spectrograph at the National Superconducting Cyclotron Laboratory at Michigan State University. Excited states in $^{56}$Cu serve as resonances in the $^{55}$Ni(p,$\gamma$)$^{56}$Cu reaction, which is a part of the rp-process in type I x-ray bursts. To resolve existing ambiguities in the reaction Q-value, a more localized IMME mass fit is used resulting in $Q=639\pm82$~keV. We derive the first experimentally-constrained thermonuclear reaction rate for $^{55}$Ni(p,$\gamma$)$^{56}$Cu. We find that, with this new rate, the rp-process may bypass the $^{56}$Ni waiting point via the $^{55}$Ni(p,$\gamma$) reaction for typical x-ray burst conditions with a branching of up to $\sim$40$\%$. We also identify additional nuclear physics uncertainties that need to be addressed before drawing final conclusions about the rp-process reaction flow in the $^{56}$Ni region.Comment: 8 pages, accepted for Phys. Rev.

Thermodynamic theory of epitaxial ferroelectric thin films with dense domain structures

A Landau-Ginsburg-Devonshire-type nonlinear phenomenological theory is presented, which enables the thermodynamic description of dense laminar polydomain states in epitaxial ferroelectric thin films. The theory explicitly takes into account the mechanical substrate effect on the polarizations and lattice strains in dissimilar elastic domains (twins). Numerical calculations are performed for PbTiO3 and BaTiO3 films grown on (001)-oriented cubic substrates. The "misfit strain-temperature" phase diagrams are developed for these films, showing stability ranges of various possible polydomain and single-domain states. Three types of polarization instabilities are revealed for polydomain epitaxial ferroelectric films, which may lead to the formation of new polydomain states forbidden in bulk crystals. The total dielectric and piezoelectric small-signal responses of polydomain films are calculated, resulting from both the volume and domain-wall contributions. For BaTiO3 films, strong dielectric anomalies are predicted at room temperature near special values of the misfit strain.Comment: 19 pages, 8 figure

Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases

The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy

Prediction of higher mortality reduction for the UK Breast Screening Frequency Trial: A model-based approach on screening intervals

Background: The optimal interval between two consecutive mammograms is uncertain. The UK Frequency Trial did not show a significant difference in breast cancer mortality between screening every year (study group) and screening every 3 years (control group). In this study, the trial is simulated in order to gain insight into the results of the trial and to predict the effect of different screening intervals on breast cancer mortality. Methods: UK incidence, life tables and information from the trial were used in the microsimulation model MISCAN-Fadia to simulate the trial and predict the number of breast ca

Organizational Culture and Physician Satisfaction with Dimensions of Group Practice

To assess the extent to which the organizational culture of physician group practices is associated with individual physician satisfaction with the managerial and organizational capabilities of the groups. Study Design and Methods . Physician surveys from 1997 to 1998 assessing the culture of their medical groups and their satisfaction with six aspects of group practice. Organizational culture was conceptualized using the Competing Values framework, yielding four distinct cultural types. Physician-level data were aggregated to the group level to attain measures of organizational culture. Using hierarchical linear modeling, individual physician satisfaction with six dimensions of group practice was predicted using physician-level variables and group-level variables. Separate models for each of the four cultural types were estimated for each of the six satisfaction measures, yielding a total of 24 models. Sample Studied . Fifty-two medical groups affiliated with 12 integrated health systems from across the U.S., involving 1,593 physician respondents (38.3 percent response rate). Larger medical groups and multispecialty groups were over-represented compared with the U.S. as a whole. Principal Findings . Our models explain up to 31 percent of the variance in individual physician satisfaction with group practice, with individual organizational culture scales explaining up to 5 percent of the variance. Group-level predictors: group (i.e., participatory) culture was positively associated with satisfaction with staff and human resources, technological sophistication, and price competition. Hierarchical (i.e., bureaucratic) culture was negatively associated with satisfaction with managerial decision making, practice level competitiveness, price competition, and financial capabilities. Rational (i.e., task-oriented) culture was negatively associated with satisfaction with staff and human resources, and price competition. Developmental (i.e., risk-taking) culture was not significantly associated with any of the satisfaction measures. In some of the models, being a single-specialty group (compared with a primary care group) and a group having a higher percent of male physicians were positively associated with satisfaction with financial capabilities. Physician-level predictors: individual physicians' ratings of organizational culture were significantly related to many of the satisfaction measures. In general, older physicians were more satisfied than younger physicians with many of the satisfaction measures. Male physicians were less satisfied with data capabilities. Primary care physicians (versus specialists) were less satisfied with price competition. Conclusion . Some dimensions of physician organizational culture are significantly associated with various aspects of individual physician satisfaction with group practice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72696/1/j.1475-6773.2006.00648.x.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/72696/2/HESR+648+Appendix+A.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/72696/3/HESR+648+Appendix+C.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/72696/4/HESR+648+Appendix+B.pd

Prognosis of screen-detected breast cancers: results of a population based study

BACKGROUND: The reduced mortality rate from breast carcinoma among women offered screening mammography is demonstrated after 15–20 years of follow-up. However, the assessment of 5-year overall and event-free survival could represent an earlier measure of the efficacy of mammography screening program (MSP). METHODS: All cases of breast cancer diagnosed in the Province of Modena between years 1996 and 2000 in women aged 50 to 69 years, were identified through the Modena Cancer Registry (MCR). Stage of disease and treatment information were obtained from clinical records. All the events occurring up to June 30, 2003 were retrieved by experienced monitors. Five-year overall and event-free survival were the principal end-points of the study. RESULTS: During a 5-year period, 587 primary breast cancers were detected by the MSP and 471 primary breast cancers were diagnosed out of the MSP. The screen-detected breast cancers were smaller, more likely node negative, with low histological grade, low proliferative activity and positive receptors status. Furthermore, the breast cancer diagnosed through the MSP more frequently received a conservative surgery. The 5-year survival rate was 94% in the screen-detected group, versus 84% in the other group (p = 0.0001). The rate of 5-year event-free survival was 89% and 75% for the MSP participants and not participants, respectively (p = 0.0001). CONCLUSIONS: Our data confirm a favourable outcome of screen-detected breast cancers in terms of five-year overall and event-free survival, which reflect the good quality assurance parameters of the MSP. Finally, a cancer registry should be implemented in every area covered by screening programs

Cost-effectiveness of stereotactic large-core needle biopsy for nonpalpable breast lesions compared to open-breast biopsy

This paper demonstrates that the introduction of large-core needle biopsy (LCNB) replacing needle-localised breast biopsy (NLBB) for nonpalpable (screen-detected) breast lesions could result in substantial cost savings at the expense of a possible slight increase in breast cancer mortality. The cost-effectiveness of LCNB and NLBB was estimated using a microsimulation model. The sensitivity of LCNB (0.97) and resource use and costs of LCNB and NLBB were derived from a multicentre consecutive cohort study among 973 women who consented in getting LCNB and NLBB, if LCNB was negative. Sensitivity analyses were performed. Replacing NLBB with LCNB would result in approximately six more breast cancer deaths per year (in a target population of 2.1 million women), or in 1000 extra life-years lost from breast cancer (effect over 100 years). The total costs of management of breast cancer (3% discounted) are estimated at £4676 million with NLBB; introducing LCNB would save £13 million. The incremental cost-effectiveness ratio of continued NLBB vs LCNB would be £12 482 per additional life-year gained (3% discounted); incremental costs range from £-21 687 (low threshold for breast biopsy) to £74 378 (high sensitivity of LCNB)