Towards a Personalised Health System

This paper presents a Personalized Healthcare System (PHS), a decision support tool that can adapt to changing conditions, such as aging and illness, in individual patients. The system consists of three components: a unique personalised profile, a collection of web based tools and a web based repository for managing interactions between clinicians and tools. The proposed system makes extensive use of software agents, both for collecting the initial information required to construct a personalized profile and for transporting the information needed to use the on-line decision support tools. The paper discusses the operation of a PHS and suggests possible implementation issues

Contact transmission of influenza virus between ferrets imposes a looser bottleneck than respiratory droplet transmission allowing propagation of antiviral resistance

Influenza viruses cause annual seasonal epidemics and occasional pandemics. It is important to elucidate the stringency of bottlenecks during transmission to shed light on mechanisms that underlie the evolution and propagation of antigenic drift, host range switching or drug resistance. The virus spreads between people by different routes, including through the air in droplets and aerosols, and by direct contact. By housing ferrets under different conditions, it is possible to mimic various routes of transmission. Here, we inoculated donor animals with a mixture of two viruses whose genomes differed by one or two reverse engineered synonymous mutations, and measured the transmission of the mixture to exposed sentinel animals. Transmission through the air imposed a tight bottleneck since most recipient animals became infected by only one virus. In contrast, a direct contact transmission chain propagated a mixture of viruses suggesting the dose transferred by this route was higher. From animals with a mixed infection of viruses that were resistant and sensitive to the antiviral drug oseltamivir, resistance was propagated through contact transmission but not by air. These data imply that transmission events with a looser bottleneck can propagate minority variants and may be an important route for influenza evolution

BRD4-BRD2 isoform switching coordinates pluripotent exit and Smad2-dependent lineage specification

Pluripotent Stem Cells (PSCs) hold great clinical potential, as they possess the capacity to differentiate into fully specialised tissues such as pancreas, liver, neurons and cardiac muscle. However, the molecular mechanisms that coordinate pluripotent exit with lineage specification remain poorly understood. To address this question, we perform a small molecule screen to systematically identify novel regulators of the Smad2 signalling network, a key determinant of PSC fate. We reveal an essential function for BET family bromodomain proteins in Smad2 activation, distinct from the role of Brd4 in pluripotency maintenance. Mechanistically, BET proteins specifically engage Nodal gene regulatory elements (NREs) to promote Nodal signalling and Smad2 developmental responses. In pluripotent cells, Brd2-Brd4 occupy NREs, but only Brd4 is required for pluripotency gene expression. Brd4 downregulation facilitates pluripotent exit and drives enhanced Brd2 NRE occupancy, thereby unveiling a specific function for Brd2 in differentiative Nodal-Smad2 signalling. Therefore, distinct BET functionalities and Brd4-Brd2 isoform switching at NREs coordinate pluripotent exit with lineage specification

Summary report of MINSIS workshop in Madrid

Recent developments on tau detection technologies and the construction of high intensity neutrino beams open the possibility of a high precision search for non-standard {\mu} - {\tau} flavour transition with neutrinos at short distances. The MINSIS - Main Injector Non-Standard Interaction Search- is a proposal under discussion to realize such precision measurement. This document contains the proceedings of the workshop which took place on 10-11 December 2009 in Madrid to discuss both the physics reach as well as the experimental requirements for this proposal.Comment: Proceedings of the MINSIS Workshop, Dec 10-11, 2009 in Madrid. 15 pages late

Very-high-energy observations of the binaries V 404 Cyg and 4U 0115+634 during giant X-ray outbursts

Transient X-ray binaries produce major outbursts in which the X-ray flux can increase over the quiescent level by factors as large as $10^7$. The low-mass X-ray binary V 404 Cyg and the high-mass system 4U 0115+634 underwent such major outbursts in June and October 2015, respectively. We present here observations at energies above hundreds of GeV with the VERITAS observatory taken during some of the brightest X-ray activity ever observed from these systems. No gamma-ray emission has been detected by VERITAS in 2.5 hours of observations of the microquasar V 404 Cyg from 2015, June 20-21. The upper flux limits derived from these observations on the gamma-ray flux above 200 GeV of F $< 4.4\times 10^{-12}$ cm$^{-2}$ s$^{-1}$ correspond to a tiny fraction (about $10^{-6}$) of the Eddington luminosity of the system, in stark contrast to that seen in the X-ray band. No gamma rays have been detected during observations of 4U 0115+634 in the period of major X-ray activity in October 2015. The flux upper limit derived from our observations is F $< 2.1\times 10^{-12}$ cm$^{-2}$ s$^{-1}$ for gamma rays above 300 GeV, setting an upper limit on the ratio of gamma-ray to X-ray luminosity of less than 4%.Comment: Accepted for publication in the Astrophysical Journa

Very-High-Energy γ\gamma-Ray Observations of the Blazar 1ES 2344+514 with VERITAS

We present very-high-energy $\gamma$-ray observations of the BL Lac object 1ES 2344+514 taken by the Very Energetic Radiation Imaging Telescope Array System (VERITAS) between 2007 and 2015. 1ES 2344+514 is detected with a statistical significance above background of $20.8\sigma$ in $47.2$ hours (livetime) of observations, making this the most comprehensive very-high-energy study of 1ES 2344+514 to date. Using these observations the temporal properties of 1ES 2344+514 are studied on short and long times scales. We fit a constant flux model to nightly- and seasonally-binned light curves and apply a fractional variability test, to determine the stability of the source on different timescales. We reject the constant-flux model for the 2007-2008 and 2014-2015 nightly-binned light curves and for the long-term seasonally-binned light curve at the $> 3\sigma$ level. The spectra of the time-averaged emission before and after correction for attenuation by the extragalactic background light are obtained. The observed time-averaged spectrum above 200 GeV is satisfactorily fitted (${\chi^2/NDF = 7.89/6}$) by a power-law function with index $\Gamma = 2.46 \pm 0.06_{stat} \pm 0.20_{sys}$ and extends to at least 8 TeV. The extragalactic-background-light-deabsorbed spectrum is adequately fit (${\chi^2/NDF = 6.73/6}$) by a power-law function with index $\Gamma = 2.15 \pm 0.06_{stat} \pm 0.20_{sys}$ while an F-test indicates that the power-law with exponential cutoff function provides a marginally-better fit ($\chi^2/NDF$ = $2.56 / 5$) at the 2.1$\sigma$ level. The source location is found to be consistent with the published radio location and its spatial extent is consistent with a point source.Comment: 7 pages, 2 figures. Published in Monthly Notices of the Royal Astronomical Societ