The non-unique Universe

The purpose of this paper is to elucidate, by means of concepts and theorems drawn from mathematical logic, the conditions under which the existence of a multiverse is a logical necessity in mathematical physics, and the implications of Godel's incompleteness theorem for theories of everything. Three conclusions are obtained in the final section: (i) the theory of the structure of our universe might be an undecidable theory, and this constitutes a potential epistemological limit for mathematical physics, but because such a theory must be complete, there is no ontological barrier to the existence of a final theory of everything; (ii) in terms of mathematical logic, there are two different types of multiverse: classes of non-isomorphic but elementarily equivalent models, and classes of model which are both non-isomorphic and elementarily inequivalent; (iii) for a hypothetical theory of everything to have only one possible model, and to thereby negate the possible existence of a multiverse, that theory must be such that it admits only a finite model

Antibody landscapes after influenza virus infection or vaccination.

We introduce the antibody landscape, a method for the quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.This is the author’s version of the work. It will be under embargo for 6 months following publication. It is posted here by permission of the AAAS for personal use, not for redistribution. The final version is available from AAAS in Science at http://www.sciencemag.org/content/346/6212/996.long

The Potential for Respiratory Droplet-Transmissible A/H5N1 Influenza Virus to Evolve in a Mammalian Host

Avian A/H5N1 influenza viruses pose a pandemic threat. As few as five amino acid substitutions, or four with reassortment, might be sufficient for mammal-to-mammal transmission through respiratory droplets. From surveillance data, we found that two of these substitutions are common in A/H5N1 viruses, and thus, some viruses might require only three additional substitutions to become transmissible via respiratory droplets between mammals. We used a mathematical model of within-host virus evolution to study factors that could increase and decrease the probability of the remaining substitutions evolving after the virus has infected a mammalian host. These factors, combined with the presence of some of these substitutions in circulating strains, make a virus evolving in nature a potentially serious threat. These results highlight critical areas in which more data are needed for assessing, and potentially averting, this threat

Influenza vaccine strain selection and recent studies on the global migration of seasonal influenza viruses

Annual influenza epidemics in humans affect 5-15% of the population, causing an estimated half million deaths worldwide per year [Stohr K. Influenza-WHO cares. Lancet Infectious Diseases 2002;2(9):517]. The virus can infect this proportion of people year after year because the virus has an extensive capacity to evolve and thus evade the immune response. For example, since the influenza A(H3N2) subtype entered the human population in 1968 the A(H3N2) component of the influenza vaccine has had to be updated almost 30 times to track the evolution of the viruses and remain effective. The World Health Organization Global Influenza Surveillance Network (WHO GISN) tracks and analyzes the evolution and epidemiology of influenza viruses for the primary purpose of vaccine strain selection and to improve the strain selection process through studies aimed at better understanding virus evolution and epidemiology. Here we give an overview of the strain selection process and outline recent investigations into the global migration of seasonal influenza viruses. (c) 2008 Published by Elsevier Ltd

The global circulation of seasonal influenza A (H3N2) viruses

Antigenic and genetic analysis of the hemagglutinin of similar to 13,000 human influenza A ( H3N2) viruses from six continents during 2002- 2007 revealed that there was continuous circulation in east and Southeast Asia ( E- SE Asia) via a region- wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A ( H3N2) viruses leave E- SE Asia, they are unlikely to contribute to long- term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A ( H3N2) viruses outside E- SE Asia may be forecast each year based on surveillance within E- SE Asia, with consequent improvements to vaccine strain selection

The global circulation of seasonal influenza A (H3N2) viruses.

Antigenic and genetic analysis of the hemagglutinin of approximately 13,000 human influenza A (H3N2) viruses from six continents during 2002-2007 revealed that there was continuous circulation in east and Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection