Homogeneous Modes of Cosmological Instantons

We discuss the O(4) invariant perturbation modes of cosmological instantons. These modes are spatially homogeneous in Lorentzian spacetime and thus not relevant to density perturbations. But their properties are important in establishing the meaning of the Euclidean path integral. If negative modes are present, the Euclidean path integral is not well defined, but may nevertheless be useful in an approximate description of the decay of an unstable state. When gravitational dynamics is included, counting negative modes requires a careful treatment of the conformal factor problem. We demonstrate that for an appropriate choice of coordinate on phase space, the second order Euclidean action is bounded below for normalized perturbations and has a finite number of negative modes. We prove that there is a negative mode for many gravitational instantons of the Hawking-Moss or Coleman-De Luccia type, and discuss the associated spectral flow. We also investigate Hawking-Turok constrained instantons, which occur in a generic inflationary model. Implementing the regularization and constraint proposed by Kirklin, Turok and Wiseman, we find that those instantons leading to substantial inflation do not possess negative modes. Using an alternate regularization and constraint motivated by reduction from five dimensions, we find a negative mode is present. These investigations shed new light on the suitability of Euclidean quantum gravity as a potential description of our universe.Comment: 16 pages, compressed and RevTex file, including one postscript figure fil

Differential Muon Tomography to Continuously Monitor Changes in the Composition of Subsurface Fluids

Muon tomography has been used to seek hidden chambers in Egyptian pyramids and image subsurface features in volcanoes. It seemed likely that it could be used to image injected, supercritical carbon dioxide as it is emplaced in porous geological structures being used for carbon sequestration, and also to check on subsequent leakage. It should work equally well in any other application where there are two fluids of different densities, such as water and oil, or carbon dioxide and heavy oil in oil reservoirs. Continuous monitoring of movement of oil and/or flood fluid during enhanced oil recovery activities for managing injection is important for economic reasons. Checking on leakage for geological carbon storage is essential both for safety and for economic purposes. Current technology (for example, repeat 3D seismic surveys) is expensive and episodic. Muons are generated by high- energy cosmic rays resulting from supernova explosions, and interact with gas molecules in the atmosphere. This innovation has produced a theoretical model of muon attenuation in the thickness of rock above and within a typical sandstone reservoir at a depth of between 1.00 and 1.25 km. Because this first simulation was focused on carbon sequestration, the innovators chose depths sufficient for the pressure there to ensure that the carbon dioxide would be supercritical. This innovation demonstrates for the first time the feasibility of using the natural cosmic-ray muon flux to generate continuous tomographic images of carbon dioxide in a storage site. The muon flux is attenuated to an extent dependent on, amongst other things, the density of the materials through which it passes. The density of supercritical carbon dioxide is only three quarters that of the brine in the reservoir that it displaces. The first realistic simulations indicate that changes as small as 0.4% in the storage site bulk density could be detected (equivalent to 7% of the porosity, in this specific case). The initial muon flux is effectively constant at the surface of the Earth. Sensitivity of the method would be decreased with increasing depth. However, sensitivity can be improved by emplacing a greater array of particle detectors at the base of the reservoir

Characterizing and minimizing the effects of noise in tide gauge time series: Relative and geocentric sea level rise around Australia

We quantify the rate of sea level rise around the Australian continent from an analysis of tidegauge and Global Positioning System (GPS) data sets. To estimate the underlying linear ratesof sea level change in the presence of significant interannual and

Clinical audit of subjects with snoring & sleep apnoea/hypopnoea syndrome fitted with mandibular repositioning splint

SummarySnoring and obstructive sleep apnoea/hypopnoea syndrome (OSAHS) are often treated with mandibular repositioning splints (MRS), but the efficacy and satisfaction of them has not been comprehensively addressed. A survey on the use of and satisfaction with MRS was posted to 177 patients referred by a hospital orthodontic department for custom-fitting of a MRS. Data were analysed using non-parametric techniques. The response rate was 81% (n=144). Responders (30F, 114M) had mean (SD) age of 51 (11) years, apnoea+hypopnoea index (AHI) of 24 (21) per hr and Epworth Score of 10 (5) at diagnosis, and had been supplied with their MRS a median 7 (IQR 5–11) months previously. Fifty of the 144 patients (35%) had been offered continuous positive airway pressure (CPAP) treatment but had declined or abandoned this. Self-reported MRS use was 5 (2) h/night, with 74 of the 144 patients (51%) continuing to use MRS at least occasionally at a median 7 months after fitting. Survival analysis showed 12% still using MRS at 12 months. Epworth score fell slightly with MRS therapy [−2.4 (3.5); P=0.005] and 7 daytime and 2 nocturnal symptoms improved in MRS users (all P<0.05). Marital satisfaction did not change with MRS. Problems preventing MRS use in 70 non-users included: non-retention (n=12), sore mouth (n=13) or jaw (n=7), difficulties falling asleep (n=10) or breathing (n=7), excessive salivation (n=4), dental damage (n=4) and other problems (n=3). Continued use of MRS therapy was associated with a higher number of teeth, low marital satisfaction perceived by partners and greater improvement in symptoms reported by patients and partners. Continuance with MRS may be low and linked to tolerance problems

Cosmological Perturbations from the No Boundary Euclidean Path Integral

We compute, from first principles, the quantum fluctuations about instanton saddle points of the Euclidean path integral for Einstein gravity coupled to a scalar field. The Euclidean two-point correlator is analytically continued into the Lorentzian region where it describes the quantum mechanical vacuum fluctuations in the state described by no boundary proposal initial conditions. We concentrate on the density perturbations in open inflationary universes produced from cosmological instantons, describing the differences between non-singular Coleman-De Luccia and singular Hawking-Turok instantons. We show how the Euclidean path integral uniquely specifies the fluctuations in both cases.Comment: 21 pages, RevTex file, including five postscript figure file

Gravity Waves from Instantons

We perform a first principles computation of the spectrum of gravity waves produced in open inflationary universes. The background spacetime is taken to be the continuation of an instanton saddle point of the Euclidean no boundary path integral. The two-point tensor correlator is computed directly from the path integral and is shown to be unique and well behaved in the infrared. We discuss the tensor contribution to the cosmic microwave background anisotropy and show how it may provide an observational discriminant between different types of primordial instantons.Comment: 19 pages, RevTex file, including two postscript figure file

Final Protocol and Statistical Analysis Plan for the SNAP Trial - a randomised, double-blind, placebo-controlled trial of nicotine replacement therapy in pregnancy

This NIHR HTA-funded smoking, nicotine and pregnancy (SNAP) trial investigated whether or not nicotine replacement therapy (NRT) is effective, cost-effective and safe when used for smoking cessation by pregnant women. We randomised 1050 women who were between 12 and 24 weeks pregnant as they attended hospital for ante-natal ultrasound scans. Women received either nicotine or placebo transdermal patches with behavioural support. The primary outcome measure was biochemically-validated, self-reported, prolonged and total abstinence from smoking between a quit date (defined before randomisation and set within 2 weeks of this) and delivery. At 6 months after childbirth self-reported maternal smoking status was ascertained and 2 years after childbirth, self-reported maternal smoking status and the behaviour, cognitive development and respiratory symptoms of children born in the trial were compared in both groups. This repository contains the final approved version of the protocol plus the statistical analysis plan (SAP) for both outcomes at delivery and following the 2 year follow up period after birth

Closed Universes from Cosmological Instantons

Current observational data is consistent with the universe being slightly closed. We investigate families of singular and non-singular closed instantons that could describe the beginning of a closed inflationary universe. We calculate the scalar and tensor perturbations that would be generated from singular instantons and compute the corresponding CMB power spectrum in a universe with cosmological parameters like our own. We investigate spatially homogeneous modes of the instantons, finding unstable modes which render the instantons sub-dominant contributions in the path integral. We show that a suitable condition may be imposed on singular closed instantons, constraining their instabilities. With this constraint these instantons can provide a suitable model of the early universe, and predict CMB power spectra in close agreement with the predictions of slow-roll inflation.Comment: 12 pages, 6 figure

Orexin receptors in GtoPdb v.2021.3

Orexin receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Orexin receptors [42]) are activated by the endogenous polypeptides orexin-A and orexin-B (also known as hypocretin-1 and -2; 33 and 28 aa) derived from a common precursor, preproorexin or orexin precursor, by proteolytic cleavage and some typical peptide modifications [109]. Currently the only orexin receptor ligands in clinical use are suvorexant and lemborexant, which are used as hypnotics. Orexin receptor crystal structures have been solved [134, 133, 54, 117, 46]