Primary care physicians' knowledge and attitudes towards genetic testing for breast-ovarian cancer predisposition

Background: Primary health care providers are expected to be directly involved in the genetic testing for cancer susceptibility. This study assessed physicians' knowledge, attitude and perception of their role towards testing for hereditary breast-ovarian cancer. Design: A mail-in survey was sent to all general practitioners, internists, obstetrician-gynecologists and oncologists in private practice in Geneva county, Switzerland. Questions included socio-demographic variables, knowledge about hereditary breast-ovarian cancer, attitude towards testing and assessment of their role in the pre- and post-test procedure. Results: Two hundred fifty-nine (65%) of four hundred questionnaires were returned of which two hundred forty-three (61%) were analysed. Response rates were similar between specialties; women answered more frequently. The majority of the respondents (87%) approved of genetic susceptibility testing. The most common objection to testing was the absence of approved strategies for the prevention and detection of early breast cancer. Most physicians felt they had an active part to play in the pre-test procedure, the disclosure of results, and especially the consultants' long-term care and support (99%). Physicians correctly answered a third (32%) of the knowledge questions. The abstention rate for individual items ranged from 13% to 60%. Scores varied by specialty. Oncologists were more knowledgeable than gynecologists, internists and general practitioners. Conclusions: The majority of the primary care physicians in this study have a favourable attitude and are ready to play a prominent role in genetic counseling and testing for breast-ovarian cancer predisposition. Defective knowledge scores, however, underline the need for targeted educational program

The curvature of semidirect product groups associated with two-component Hunter-Saxton systems

In this paper, we study two-component versions of the periodic Hunter-Saxton equation and its $\mu$-variant. Considering both equations as a geodesic flow on the semidirect product of the circle diffeomorphism group \Diff(\S) with a space of scalar functions on $\S$ we show that both equations are locally well-posed. The main result of the paper is that the sectional curvature associated with the 2HS is constant and positive and that 2$\mu$HS allows for a large subspace of positive sectional curvature. The issues of this paper are related to some of the results for 2CH and 2DP presented in [J. Escher, M. Kohlmann, and J. Lenells, J. Geom. Phys. 61 (2011), 436-452].Comment: 19 page

Coupled-channels calculations of nonelastic cross sections using a density-functional structure model

A microscopic calculation of the reaction cross-section for nucleon-nucleus scattering has been performed by explicitly coupling the elastic channel to all particle-hole (p-h) excitation states in the target and to all one-nucleon pickup channels. The p-h states may be regarded as doorway states through which the flux flows to more complicated configurations, and subsequently to long-lived compound nucleus resonances. Target excitations for 40,48Ca, 58Ni, 90Zr and 144Sm were described in a QRPA framework using a Skyrme functional. Reaction cross sections calculated in this approach were compared to predictions of a fitted optical potential and to experimental data, reaching very good agreement. Couplings between inelastic states were found to be negligible, while the couplings to pickup channels contribute significantly. For the first time observed reaction cross-sections are completely accounted for by explicit channel coupling, for incident energies between 10 and 40 MeV.Comment: Accepted for publication on Physical Review Letters. Article is expected to be published in the November 12, 2010 issue. 4 pages, 4 figure

The geometry of a vorticity model equation

We provide rigorous evidence of the fact that the modified Constantin-Lax-Majda equation modeling vortex and quasi-geostrophic dynamics describes the geodesic flow on the subgroup of orientation-preserving diffeomorphisms fixing one point, with respect to right-invariant metric induced by the homogeneous Sobolev norm $H^{1/2}$ and show the local existence of the geodesics in the extended group of diffeomorphisms of Sobolev class $H^{k}$ with $k\ge 2$.Comment: 24 page

Reaction cross-section predictions for nucleon induced reactions

A microscopic calculation of the optical potential for nucleon-nucleus scattering has been performed by explicitly coupling the elastic channel to all the particle-hole (p-h) excitation states in the target and to all relevant pickup channels. These p-h states may be regarded as doorway states through which the flux flows to more complicated configurations, and to long-lived compound nucleus resonances. We calculated the reaction cross sections for the nucleon induced reactions on the targets $^{40,48}$Ca, $^{58}$Ni, $^{90}$Zr and $^{144}$Sm using the QRPA description of target excitations, coupling to all inelastic open channels, and coupling to all transfer channels corresponding to the formation of a deuteron. The results of such calculations were compared to predictions of a well-established optical potential and with experimental data, reaching very good agreement. The inclusion of couplings to pickup channels were an important contribution to the absorption. For the first time, calculations of excitations account for all of the observed reaction cross-sections, at least for incident energies above 10 MeV.Comment: 6 pages, 6 figures. Submitted to INPC 2010 Conference Proceeding

Absence of squirt singularities for the multi-phase Muskat problem

In this paper we study the evolution of multiple fluids with different constant densities in porous media. This physical scenario is known as the Muskat and the (multi-phase) Hele-Shaw problems. In this context we prove that the fluids do not develop squirt singularities.Comment: 16 page

Breakdown of smoothness for the Muskat problem

In this paper we show that there exist analytic initial data in the stable regime for the Muskat problem such that the solution turns to the unstable regime and later breaks down i.e. no longer belongs to $C^4$.Comment: 93 pages, 10 figures (6 added

Modifier Genes as Therapeutics: The Nuclear Hormone Receptor Rev Erb Alpha (Nr1d1) Rescues Nr2e3 Associated Retinal Disease

Nuclear hormone receptors play a major role in many important biological processes. Most nuclear hormone receptors are ubiquitously expressed and regulate processes such as metabolism, circadian function, and development. They function in these processes to maintain homeostasis through modulation of transcriptional gene networks. In this study we evaluate the effectiveness of a nuclear hormone receptor gene to modulate retinal degeneration and restore the integrity of the retina. Currently, there are no effective treatment options for retinal degenerative diseases leading to progressive and irreversible blindness. In this study we demonstrate that the nuclear hormone receptor gene Nr1d1 (Rev-Erba) rescues Nr2e3- associated retinal degeneration in the rd7 mouse, which lacks a functional Nr2e3 gene. Mutations in human NR2E3 are associated with several retinal degenerations including enhanced S cone syndrome and retinitis pigmentosa. The rd7 mouse, lacking Nr2e3, exhibits an increase in S cones and slow, progressive retinal degeneration. A traditional genetic mapping approach previously identified candidate modifier loci. Here, we demonstrate that in vivo delivery of the candidate modifier gene, Nr1d1 rescues Nr2e3 associated retinal degeneration. We observed clinical, histological, functional, and molecular restoration of the rd7 retina. Furthermore, we demonstrate that the mechanism of rescue at the molecular and functional level is through the re-regulation of key genes within the Nr2e3-directed transcriptional network. Together, these findings reveal the potency of nuclear receptors as modulators of disease and specifically of NR1D1 as a novel therapeutic for retinal degenerations