Anisotropic Inflation from Extra Dimensions

Vacuum multidimensional cosmological models with internal spaces being compact $n$-dimensional Lie group manifolds are considered. Products of 3-spheres and $SU(3)$ manifold (a novelty in cosmology) are studied. It turns out that the dynamical evolution of the internal space drives an accelerated expansion of the external world (power law inflation). This generic solution (attractor in a phase space) is determined by the Lie group space without any fine tuning or arbitrary inflaton potentials. Matter in the four dimensions appears in the form of a number of scalar fields representing anisotropic scale factors for the internal space. Along the attractor solution the volume of the internal space grows logarithmically in time. This simple and natural model should be completed by mechanisms terminating the inflationary evolution and transforming the geometric scalar fields into ordinary particles.Comment: LaTeX, 11 pages, 5 figures available via fax on request to [email protected], submitted to Phys. Lett.

Inflation in Multidimensional Quantum Cosmology

We extend to multidimensional cosmology Vilenkin's prescription of tunnelling from nothing for the quantum origin of the observable Universe. Our model consists of a $D+4$-dimensional spacetime of topology ${\cal R}\times {\cal S}^3 \times{\cal S}^D$, with a scalar field (``chaotic inflaton'') for the matter component. Einstein gravity and Casimir compactification are assumed. The resulting minisuperspace is 3--dimensional. Patchwise we find an approximate analytic solution of the Wheeler--DeWitt equation through which we discuss the tunnelling picture and the probability of nucleation of the classical Universe with compactifying extra dimensions. Our conclusion is that the most likely initial conditions, although they do not lead to the compactification of the internal space, still yield (power-law) inflation for the outer space. The scenario is physically acceptable because the inner space growth is limited to $\sim 10^{11}$ in 100 e-foldings of inflation, starting from the Planck scale.Comment: RevTeX, 30 pages, 4 figures available via fax on request to [email protected], submitted to Phys. Rev.

Graviton Spectra in String Cosmology

We propose to uncover the signature of a stringy era in the primordial Universe by searching for a prominent peak in the relic graviton spectrum. This feature, which in our specific model terminates an $\omega^3$ increase and initiates an $\omega^{-7}$ decrease, is induced during the so far overlooked bounce of the scale factor between the collapsing deflationary era (or pre-Big Bang) and the expanding inflationary era (or post-Big Bang). We evaluate both analytically and numerically the frequency and the intensity of the peak and we show that they may likely fall in the realm of the new generation of interferometric detectors. The existence of a peak is at variance with ordinarily monotonic (either increasing or decreasing) graviton spectra of canonical cosmologies; its detection would therefore offer strong support to string cosmology.Comment: 14 pages, RevTex source and 6 figures.p

Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom

Aim: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). Methods: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. Results: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. Conclusions: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS