Towards elimination of Hepatitis C in Vietnam

Vietnam has a high burden of viral hepatitis. This thesis strives to advance its elimination, addressing important gaps in the literature that I hope will contribute to treatment guidelines and health policy, both in Vietnam and internationally. Firstly, to define the hepatitis epidemic in Vietnam, I assimilate all published seroprevalence data since 1990 to estimate pooled prevalence of HBV, HCV and HDV in high and low risk populations. I show that although blood safety has improved, and HDV is largely confined to high-risk populations, a renewed focus on birth dose HBV vaccination and targeted HCV screening and treatment of people who inject drugs, is urgently required to meet elimination targets. The next chapters address HCV therapy, namely predictive factors for selecting individuals who could be treated for shorter duration, treatment failure in relation to rare HCV subtypes, and the clinical importance of resistance mutations. I describe a prospective clinical trial evaluating the efficacy of shortened sofosbuvir and daclatasvir therapy, based on early virological response: firstly, in genotype 1 or 6-infected individuals with mild disease (chapter 3) and then in genotype 6-infected individuals with advanced liver fibrosis (chapter 4). I show that shortened therapy, with retreatment if needed, can reduce antiviral use while maintaining high cure rates, but that day 2 virologic response alone is not an adequate predictor of cure. I demonstrate that a high frequency of putative NS5A inhibitor resistance mutations in genotype 6 infection does not impact cure rates, negating the need for costly genotyping in Vietnam. In my final data chapter, I explore an innovative means of decentralising HCV care. In two independent study populations from Vietnam and the UK, I show that an increase in routinely taken alanine transaminase after HCV therapy is a reliable screen for treatment failure that could substantially reduce reliance on nucleic acid testing in remote and resource-limited settings.Open Acces

Observable non-gaussianity from gauge field production in slow roll inflation, and a challenging connection with magnetogenesis

In any realistic particle physics model of inflation, the inflaton can be expected to couple to other fields. We consider a model with a dilaton-like coupling between a U(1) gauge field and a scalar inflaton. We show that this coupling can result in observable non-gaussianity, even in the conventional regime where inflation is supported by a single scalar slowly rolling on a smooth potential: the time dependent inflaton condensate leads to amplification of the large-scale gauge field fluctuations, which can feed-back into the scalar/tensor cosmological perturbations. In the squeezed limit, the resulting bispectrum is close to the local one, but it shows a sizable and characteristic quadrupolar dependence on the angle between the shorter and the larger modes in the correlation. Observable non-gaussianity is obtained in a regime where perturbation theory is under control. If the gauge field is identified with the electromagnetic field, the model that we study is a realization of the magnetogenesis idea originally proposed by Ratra, and widely studied. This identification (which is not necessary for the non-gaussianity production) is however problematic in light of a strong coupling problem already noted in the literature.Comment: 28 pages, no figures. Final versio

Phenomenology of a Pseudo-Scalar Inflaton: Naturally Large Nongaussianity

Many controlled realizations of chaotic inflation employ pseudo-scalar axions. Pseudo-scalars \phi are naturally coupled to gauge fields through c \phi F \tilde{F}. In the presence of this coupling, gauge field quanta are copiously produced by the rolling inflaton. The produced gauge quanta, in turn, source inflaton fluctuations via inverse decay. These new cosmological perturbations add incoherently with the "vacuum" perturbations, and are highly nongaussian. This provides a natural mechanism to generate large nongaussianity in single or multi field slow-roll inflation. The resulting phenomenological signatures are highly distinctive: large nongaussianity of (nearly) equilateral shape, in addition to detectably large values of both the scalar spectral tilt and tensor-to-scalar ratio (both being typical of large field inflation). The WMAP bound on nongaussianity implies that the coupling, c, of the pseudo-scalar inflaton to any gauge field must be smaller than about 10^{2} M_p^{-1}.Comment: 45 pages, 7 figure

Inhomogeneous tachyon condensation

We investigate the spacetime-dependent condensation of the tachyon in effective field theories. Previous work identified singularities in the field which appear in finite time: infinite gradients at the kinks, and (in the eikonal approximation) caustics near local minima. By performing a perturbation analysis, and with numerical simulations, we demonstrate and explain key features of the condensation process: perturbations generically freeze, and minima develop singular second derivatives in finite time (caustics). This last has previously been understood in terms of the eikonal approximation to the dynamics. We show explicitly from the field equations how this approximation emerges, and how the caustics develop, both in the DBI and BSFT effective actions. We also investigate the equation of state parameter of tachyon matter showing that it is small, but generically non-zero. The energy density tends to infinity near field minima with a charateristic profile. A proposal to regulate infinities by modifying the effective action is also studied. We find that although the infinities at the kinks are successfully regularised in the time-dependent case, caustics still present.Comment: 4 figures,19p

Preheating After Modular Inflation

We study (p)reheating in modular (closed string) inflationary scenarios, with a special emphasis on Kahler moduli/Roulette models. It is usually assumed that reheating in such models occurs through perturbative decays. However, we find that there are very strong non-perturbative preheating decay channels related to the particular shape of the inflaton potential (which is highly nonlinear and has a very steep minimum). Preheating after modular inflation, proceeding through a combination of tachyonic instability and broad-band parametric resonance, is perhaps the most violent example of preheating after inflation known in the literature. Further, we consider the subsequent transfer of energy to the standard model sector in scenarios where the standard model particles are confined to a D7-brane wrapping the inflationary blow-up cycle of the compactification manifold or, more interestingly, a non-inflationary blow up cycle. We explicitly identify the decay channels of the inflaton in these two scenarios. We also consider the case where the inflationary cycle shrinks to the string scale at the end of inflation; here a field theoretical treatment of reheating is insufficient and one must turn instead to a stringy description. We estimate the decay rate of the inflaton and the reheat temperature for various scenarios.Comment: 34 pages, 10 figures. Accepted for publication in JCA

Cosmological Fluctuations from Infra-Red Cascading During Inflation

We propose a qualitatively new mechanism for generating cosmological fluctuations from inflation. The non-equilibrium excitation of interacting scalar fields often evolves into infra-red (IR) and ultra-violet (UV) cascading, resulting in an intermediate scaling regime. We observe elements of this phenomenon in a simple model with inflaton \phi and iso-inflaton \chi fields interacting during inflation via the coupling g^2 (\phi-\phi_0)^2 \chi^2. Iso-inflaton particles are created during inflation when they become instantaneously massless at \phi=\phi_0, with occupation numbers not exceeding unity. We point out that very quickly the produced \chi particles become heavy and their multiple re-scatterings off the homogeneous condensate \phi(t) generates bremschtrahlung radiation of light inflaton IR fluctuations with high occupation numbers. The subsequent evolution of these IR fluctuations is qualitatively similar to that of the usual inflationary fluctuations, but their initial amplitude is different. The IR cascading generates a bump-shaped contribution to the cosmological curvature fluctuations, which can even dominate over the usual fluctuations for g^2>0.06. The IR cascading curvature fluctuations are significantly non-gaussian and the strength and location of the bump are model-dependent, through g^2 and \phi_0. The effect from IR cascading fluctuations is significantly larger than that from the momentary slowing-down of \phi(t). With a sequence of such bursts of particle production, the superposition of the bumps can lead to a new broad band non-gaussian component of cosmological fluctuations added to the usual fluctuations. Such a sequence of particle creation events can, but need not, lead to trapped inflation.Comment: 13 pages, 9 figures. Accepted for publication in Phys. Rev.

Towards a Resolution of the Cosmological Singularity in Non-local Higher Derivative Theories of Gravity

One of the greatest problems of standard cosmology is the Big Bang singularity. Previously it has been shown that non-local ghostfree higher-derivative modifications of Einstein gravity in the ultra-violet regime can admit non-singular bouncing solutions. In this paper we study in more details the dynamical properties of the equations of motion for these theories of gravity in presence of positive and negative cosmological constants and radiation. We find stable inflationary attractor solutions in the presence of a positive cosmological constant which renders inflation {\it geodesically complete}, while in the presence of a negative cosmological constant a cyclic universe emerges. We also provide an algorithm for tracking the super-Hubble perturbations during the bounce and show that the bouncing solutions are free from any perturbative instability.Comment: 38 pages, 6 figures. V2: Added: a word to the title, clarifications, an appendix, many references. To appear in JCA

FRW Cosmology with Non-positively Defined Higgs Potentials

We discuss the classical aspects of dynamics of scalar models with non-positive Higgs potentials in the FRW cosmology. These models appear as effective local models in non-local models related with string field theories. After a suitable field redefinition these models have the form of local Higgs models with a negative extra cosmological term and the total Higgs potential is non-positively defined and has rather small coupling constant. The non-positivity of the potential leads to the fact that on some stage of evolution the expansion mode gives place to the mode of contraction, due to that the stage of reheating is absent. In these models the hard regime of inflation gives place to inflation near the hill top and the area of the slow roll inflation is very small. Meanwhile one can obtain enough e-foldings before the contraction to make the model under consideration admissible to describe inflation.Comment: 40 pages, 20 figures, typos correcte

Localization of the SFT inspired Nonlocal Linear Models and Exact Solutions

A general class of gravitational models driven by a nonlocal scalar field with a linear or quadratic potential is considered. We study the action with an arbitrary analytic function $F(\Box)$, which has both simple and double roots. The way of localization of nonlocal Einstein equations is generalized on models with linear potentials. Exact solutions in the Friedmann-Robertson-Walker and Bianchi I metrics are presented.Comment: 20 pages, 3 figures, published in the proceedings of the VIII International Workshop "Supersymmetries and Quantum Symmetries" (SQS'09), Dubna, Russia, July 29 - August 3, 2009, http://theor.jinr.ru/~sqs09