How genomic information is accessed in clinical practice: an electronic survey of UK general practitioners.

Genomic technologies are having an increasing impact across medicine, including primary care. To enable their wider adoption and realize their potential, education of primary health-care practitioners will be required. To enable the development of such resources, understanding where GPs currently access genomic information is needed. One-hundred fifty-nine UK GPs completed the survey in response to an open invitation, between September 2017 and September 2018. Questions were in response to 4 clinical genomic scenarios, with further questions exploring resources used for rare disease patients, direct-to-consumer genetic testing and collecting a family history. Respondents were most commonly GP principals (independent GPs who own their clinic) (64.8%), aged 35-49 years (54%), worked as a GP for more than 15 years (44%) and practiced within suburban locations (typically wealthier) (50.3%). The most popular 'just in time' education source for all clinical genomic scenarios were online primary care focussed resources with general Internet search engines also popular. For genomic continuous medical education, over 70% of respondents preferred online learning. Considering specific scenarios, local guidelines were a popular resource for the familial breast cancer scenario. A large proportion (41%) had not heard of Genomics England's 100,000 genome project. Few respondents (4%) would access rare disease specific Internet resources (Orphanet, OMIM). Twenty-five percent of respondents were unsure how to respond to a direct-to-consumer commercial genetic test query, with 41% forwarding such queries to local genetic services. GPs require concise, relevant, primary care focussed resources in trusted and familiar online repositories of information. Inadequate genetic education of GPs could increase burden on local genetic services

Unified first law of black-hole dynamics and relativistic thermodynamics

A unified first law of black-hole dynamics and relativistic thermodynamics is derived in spherically symmetric general relativity. This equation expresses the gradient of the active gravitational energy E according to the Einstein equation, divided into energy-supply and work terms. Projecting the equation along the flow of thermodynamic matter and along the trapping horizon of a blackhole yield, respectively, first laws of relativistic thermodynamics and black-hole dynamics. In the black-hole case, this first law has the same form as the first law of black-hole statics, with static perturbations replaced by the derivative along the horizon. There is the expected term involving the area and surface gravity, where the dynamic surface gravity is defined as in the static case but using the Kodama vector and trapping horizon. This surface gravity vanishes for degenerate trapping horizons and satisfies certain expected inequalities involving the area and energy. In the thermodynamic case, the quasi-local first law has the same form, apart from a relativistic factor, as the classical first law of thermodynamics, involving heat supply and hydrodynamic work, but with E replacing the internal energy. Expanding E in the Newtonian limit shows that it incorporates the Newtonian mass, kinetic energy, gravitational potential energy and thermal energy. There is also a weak type of unified zeroth law: a Gibbs-like definition of thermal equilibrium requires constancy of an effective temperature, generalising the Tolman condition and the particular case of Hawking radiation, while gravithermal equilibrium further requires constancy of surface gravity. Finally, it is suggested that the energy operator of spherically symmetric quantum gravity is determined by the Kodama vector, which encodes a dynamic time related to E.Comment: 18 pages, TeX, expanded somewhat, to appear in Class. Quantum Gra

Construction and enlargement of traversable wormholes from Schwarzschild black holes

Analytic solutions are presented which describe the construction of a traversable wormhole from a Schwarzschild black hole, and the enlargement of such a wormhole, in Einstein gravity. The matter model is pure radiation which may have negative energy density (phantom or ghost radiation) and the idealization of impulsive radiation (infinitesimally thin null shells) is employed.Comment: 22 pages, 7 figure

Quasi-spherical approximation for rotating black holes

We numerically implement a quasi-spherical approximation scheme for computing gravitational waveforms for coalescing black holes, testing it against angular momentum by applying it to Kerr black holes. As error measures, we take the conformal strain and specific energy due to spurious gravitational radiation. The strain is found to be monotonic rather than wavelike. The specific energy is found to be at least an order of magnitude smaller than the 1% level expected from typical black-hole collisions, for angular momentum up to at least 70% of the maximum, for an initial surface as close as $r=3m$.Comment: revised version, 8 pages, RevTeX, 8 figures, epsf.sty, psfrag.sty, graphicx.st

Plasma retinol, beta-carotene and vitamin E levels in relation to the future risk of breast cancer.

In a prospective study of 5,004 women in Guernsey, plasma samples were collected and stored. Retinol, beta-carotene and vitamin E levels were later measured in the samples from 39 women who subsequently developed breast cancer and from 78 controls who did not develop cancer. Plasma retinol levels were not related to the risk of breast cancer, mean levels among cases and controls being 485 micrograms l-1 and 479 micrograms l-1 respectively. Plasma vitamin E levels showed a clear association, low levels being associated with a significantly higher risk of cancer. The mean vitamin E levels among cases and controls were 4.7 mg l-1 and 6.0 mg l-1 respectively (P less than 0.025), and the risk of breast cancer in women with vitamin E levels in the lowest quintile was about 5-times higher than the risk for women with levels in the highest quintile (P less than 0.01). beta-carotene levels showed a tendency to be lower in women who developed cancer than in controls (36 micrograms l-1 among cases compared with 50 micrograms l-1 among controls) but the difference was not statistically significant

Gravitational waves, black holes and cosmic strings in cylindrical symmetry

Gravitational waves in cylindrically symmetric Einstein gravity are described by an effective energy tensor with the same form as that of a massless Klein- Gordon field, in terms of a gravitational potential generalizing the Newtonian potential. Energy-momentum vectors for the gravitational waves and matter are defined with respect to a canonical flow of time. The combined energy-momentum is covariantly conserved, the corresponding charge being the modified Thorne energy. Energy conservation is formulated as the first law expressing the gradient of the energy as work and energy-supply terms, including the energy flux of the gravitational waves. Projecting this equation along a trapping horizon yields a first law of black-hole dynamics containing the expected term involving area and surface gravity, where the dynamic surface gravity is defined with respect to the canonical flow of time. A first law for dynamic cosmic strings also follows. The Einstein equation is written as three wave equations plus the first law, each with sources determined by the combined energy tensor of the matter and gravitational waves.Comment: 10 pages, revtex. Published version with further detail

Production and decay of evolving horizons

We consider a simple physical model for an evolving horizon that is strongly interacting with its environment, exchanging arbitrarily large quantities of matter with its environment in the form of both infalling material and outgoing Hawking radiation. We permit fluxes of both lightlike and timelike particles to cross the horizon, and ask how the horizon grows and shrinks in response to such flows. We place a premium on providing a clear and straightforward exposition with simple formulae. To be able to handle such a highly dynamical situation in a simple manner we make one significant physical restriction, that of spherical symmetry, and two technical mathematical restrictions: (1) We choose to slice the spacetime in such a way that the space-time foliations (and hence the horizons) are always spherically symmetric. (2) Furthermore we adopt Painleve-Gullstrand coordinates (which are well suited to the problem because they are nonsingular at the horizon) in order to simplify the relevant calculations. We find particularly simple forms for surface gravity, and for the first and second law of black hole thermodynamics, in this general evolving horizon situation. Furthermore we relate our results to Hawking's apparent horizon, Ashtekar et al's isolated and dynamical horizons, and Hayward's trapping horizons. The evolving black hole model discussed here will be of interest, both from an astrophysical viewpoint in terms of discussing growing black holes, and from a purely theoretical viewpoint in discussing black hole evaporation via Hawking radiation.Comment: 25 pages, uses iopart.cls V2: 5 references added; minor typos; V3: some additional clarifications, additional references, additional appendix on the Viadya spacetime. This version published in Classical and Quiantum Gravit

The suppression of superconductivity in MgCNi3 by Ni-site doping

The effects of partial substitution of Cu and Co for Ni in the intermetallic perovskite superconductor MgCNi3 are reported. Calculation of the expected electronic density of states suggests that electron (Cu) and hole (Co) doping should have different effects. For MgCNi3-xCux, solubility of Cu is limited to approximately 3% (x = 0.1), and Tc decreases systematically from 7K to 6K. For MgCNi3-xCox, solubility of Co is much more extensive, but bulk superconductivity disappears for Co doping of 1% (x = 0.03). No signature of long range magnetic ordering is observed in the magnetic susceptibility of the Co doped material.Comment: submitted, Solid State Communication

Massive sulfide Zn deposits in the Proterozoic did not require euxinia

Our most important Zn resources occur within clastic-dominated (CD-type) deposits, which are located in a small number of Proterozoic and Phanerozoic sedimentary basins. The most common model for CD-type mineralisation involves sedimentary exhalative (SEDEX) processes, i.e. the venting of metal bearing fluids into a restricted, anoxic H2S-bearing (euxinic) water column. In the Carpentaria Zn Province (Australia), multiple world class deposits are hosted in Proterozoic (1.6 Ga) stratigraphy, where models of the ancient sulfur cycle have also been developed. Focusing on the most recent discovery – the Teena deposit – we report bulk rock and isotopic data (δ34Spyrite values) that provide information on the sulfur cycle during the diagenetic and hydrothermal evolution of the Teena sub-basin. In contrast to the SEDEX model, intervals containing abundant pyrite with highly positive δ34S values (>25 ‰) correspond with euxinic conditions that developed due to high organic loading (i.e. productivity) and not basin restriction. This basin wide feature, which can also be mistaken as a hydrothermal pyrite halo, is genetically unrelated to the subsequent hydrothermal mineralisation that formed beneath the palaeo-seafloor. The formation of CD-type deposits in the Proterozoic does not, therefore, require euxinic conditions