PUK26 THE INFLUENCE OF FUTURE UNRELATED COSTS ON COSTEFFECTIVENESS ESTIMATES:TREATMENT OF HYPERPHOSPHATEMIA WITH LANTHANUM CARBONATE IN PRE-DIALYIS PATIENTS WITH CHRONIC KIDNEY DISEASE

OBJECTIVES: A long-standing controversy in health-economics is whether future unrelated costs should be included in cost-effectiveness analyses. This discussion is relevant in Chronic Kidney Disease (CKD) for treatments that delay progression towards dialysis and prolong survival. In this study, we determined the influence of future unrelated costs on the cost-effectiveness of the non-calcium based phosphate binder lanthanum carbonate (LC) when used as second-line treatment for hyperphosphatemia in predialysis patients. METHODS: Time-dependent Markov models were constructed; cohorts of 1000 patients were followed lifelong. Patients not reaching target serum phosphate (SP) levels on first-line calcium based phosphate binders (CB) were treated with LC. This strategy was compared with continued CB treatment. Patient-level data were pooled from two clinical trials, one in predialysis and one in dialysis. Reductions in SP levels delayed progression towards dialysis and prolonged survival. RESULTS: For the predialysis cohort, 544 did not achieve target SP levels

Sculpting the Extra Dimensions: Inflation from Codimension-2 Brane Back-reaction

We construct an inflationary model in 6D supergravity that is based on explicit time-dependent solutions to the full higher-dimensional field equations, back-reacting to the presence of a 4D inflaton rolling on a space-filling codimension-2 source brane. Fluxes in the bulk stabilize all moduli except the `breathing' modulus (that is generically present in higher-dimensional supergravities). Back-reaction to the inflaton roll causes the 4D Einstein-frame on-brane geometry to expand, a(t) ~ t^p, as well as exciting the breathing mode and causing the two off-brane dimensions to expand, r(t) ~ t^q. The model evades the general no-go theorems precluding 4D de Sitter solutions, since adjustments to the brane-localized inflaton potential allow the power p to be dialed to be arbitrarily large, with the 4D geometry becoming de Sitter in the limit p -> infinity (in which case q = 0). Slow-roll solutions give accelerated expansion with p large but finite, and q = 1/2. Because the extra dimensions expand during inflation, the present-day 6D gravity scale can be much smaller than it was when primordial fluctuations were generated - potentially allowing TeV gravity now to be consistent with the much higher gravity scale required at horizon-exit for observable primordial gravity waves. Because p >> q, the 4 on-brane dimensions expand more quickly than the 2 off-brane ones, providing a framework for understanding why the observed four dimensions are presently so much larger than the internal two. If uplifted to a 10D framework with 4 dimensions stabilized, the 6D evolution described here could describe how two of the six extra dimensions evolve to become much larger than the others, as a consequence of the enormous expansion of the 4 large dimensions we can see.Comment: 27 pages + appendices, 2 figure

Supersymmetric codimension-two branes in six-dimensional gauged supergravity

We consider the six-dimensional Salam-Sezgin supergravity in the presence of codimension-2 branes. In the case that the branes carry only tension, we provide a way to supersymmetrise them by adding appropriate localised Fayet-Iliopoulos terms and localised corrections to the Chern-Simons term and modifying accordingly the fermionic supersymmetry transformations. The resulting brane action has N=1 supersymmetry (SUSY). We find the axisymmetric vacua of the system and show that one has unwarped background solutions with "football"-shaped extra dimensions which always respect N=1 SUSY for any value of the equal brane tensions, in contrast with the non-supersymmetric brane action background. Finally, we generically find multiple zero modes of the gravitino in this background and discuss how one could obtain a single chiral zero mode present in the low energy spectrum.Comment: 21 pages, no figures, A sign error in the gauge potential at the lower brane corrected and its consequent effect discusse

Long-term feeding ecology and habitat use in harbour porpoises <i>Phocoena phocoena</i> from Scandinavian waters inferred from trace elements and stable isotopes

Background. We investigated the feeding ecology and habitat use of 32 harbour porpoises by-caught in 4 localities along the Scandinavian coast from the North Sea to the Barents Sea using time-integrative markers: stable isotopes (δ13C, δ15N) and trace elements (Zn, Cu, Fe, Se, total Hg and Cd), in relation to habitat characteristics (bathymetry) and geographic position (latitude). Results. Among the trace elements analysed, only Cd, with an oceanic specific food origin, was found to be useful as an ecological tracer. All other trace elements studied were not useful, most likely because of physiological regulation and/or few specific sources in the food web. The δ13C, δ15N signatures and Cd levels were highly correlated with each other, as well as with local bathymetry and geographic position (latitude). Variation in the isotopic ratios indicated a shift in harbour porpoise's feeding habits from pelagic prey species in deep northern waters to more coastal and/or demersal prey in the relatively shallow North Sea and Skagerrak waters. This result is consistent with stomach content analyses found in the literature. This shift was associated with a northward Cd-enrichment which provides further support to the Cd 'anomaly' previously reported in polar waters and suggests that porpoises in deep northern waters include Cd-contaminated prey in their diet, such as oceanic cephalopods. Conclusion. As stable isotopes and Cd provide information in the medium and the long term respectively, the spatial variation found, shows that harbour porpoises experience different ecological regimes during the year along the Scandinavian coasts, adapting their feeding habits to local oceanographic conditions, without performing extensive migration

The vacuum bubbles in de Sitter background and black hole pair creation

We study the possible types of the nucleation of vacuum bubbles. We classify vacuum bubbles in de Sitter background and present some numerical solutions. The thin-wall approximation is employed to obtain the nucleation rate and the radius of vacuum bubbles. With careful analysis we confirm that Parke's formula is also applicable to the large true vacuum bubbles. The nucleation of the false vacuum bubble in de Sitter background is also evaluated. The tunneling process in the potential with degenerate vacua is analyzed as the limiting cases of the large true vacuum bubble and false vacuum bubble. Next, we consider the pair creation of black holes in the background of bubble solutions. We obtain static bubble wall solutions of junction equation with black hole pair. The masses of created black holes are uniquely determined by the cosmological constant and surface tension on the wall. Finally, we obtain the rate of pair creation of black holes.Comment: 3 figures, minor including errors and typos corrected, and refs. adde

Kicking the Rugby Ball: Perturbations of 6D Gauged Chiral Supergravity

We analyze the axially-symmetric scalar perturbations of 6D chiral gauged supergravity compactified on the general warped geometries in the presence of two source branes. We find all of the conical geometries are marginally stable for normalizable perturbations (in disagreement with some recent calculations) and the nonconical for regular perturbations, even though none of them are supersymmetric (apart from the trivial Salam-Sezgin solution, for which there are no source branes). The marginal direction is the one whose presence is required by the classical scaling property of the field equations, and all other modes have positive squared mass. In the special case of the conical solutions, including (but not restricted to) the unwarped `rugby-ball' solutions, we find closed-form expressions for the mode functions in terms of Legendre and Hypergeometric functions. In so doing we show how to match the asymptotic near-brane form for the solution to the physics of the source branes, and thereby how to physically interpret perturbations which can be singular at the brane positions.Comment: 21 pages + appendices, references adde

Chronology Protection in Galileon Models and Massive Gravity

Galileon models are a class of effective field theories that have recently received much attention. They arise in the decoupling limit of theories of massive gravity, and in some cases they have been treated in their own right as scalar field theories with a specific nonlinearly realized global symmetry (Galilean transformation). It is well known that in the presence of a source, these Galileon theories admit superluminal propagating solutions, implying that as quantum field theories they must admit a different notion of causality than standard local Lorentz invariant theories. We show that in these theories it is easy to construct closed timelike curves (CTCs) within the {\it naive} regime of validity of the effective field theory. However, on closer inspection we see that the CTCs could never arise since the Galileon inevitably becomes infinitely strongly coupled at the onset of the formation of a CTC. This implies an infinite amount of backreaction, first on the background for the Galileon field, signaling the break down of the effective field theory, and subsequently on the spacetime geometry, forbidding the formation of the CTC. Furthermore the background solution required to create CTCs becomes unstable with an arbitrarily fast decay time. Thus Galileon theories satisfy a direct analogue of Hawking's chronology protection conjecture.Comment: 34 pages, no figure