Transmission tree of the highly pathogenic avian influenza (H5N1) epidemic in Israel, 2015

The transmission tree of the Israeli 2015 epidemic of highly pathogenic avian influenza (H5N1) was modelled by combining the spatio-temporal distribution of the outbreaks and the genetic distance between virus isolates. The most likely successions of transmission events were determined and transmission parameters were estimated. It was found that the median infectious pressure exerted at 1 km was 1.59 times (95% CI 1.04, 6.01) and 3.54 times (95% CI 1.09, 131.75) higher than that exerted at 2 and 5 km, respectively, and that three farms were responsible for all seven transmission events. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-016-0393-2) contains supplementary material, which is available to authorized users

Prediction of specific biomolecule adsorption on silica surfaces as a function of pH and particle size

Silica nanostructures are biologically available and find wide applications for drug delivery, catalysts, separation processes, and composites. However, specific adsorption of biomolecules on silica surfaces and control in biomimetic synthesis remain largely unpredictable. In this contribution, the variability and control of peptide adsorption on silica nanoparticle surfaces is explained as a function of pH, particle diameter, and peptide electrostatic charge using molecular dynamics simulations with the CHARMM-INTERFACE force field. Adsorption free energies and specific binding residues are analyzed in molecular detail, providing experimentally elusive, atomic-level information on the complex dynamics of aqueous electric double layers in contact with biological molecules. Tunable contributions to adsorption are described in the context of specific silica surface chemistry, including ion pairing, hydrogen bonds, hydrophobic interactions, and conformation effects. Remarkable agreement is found for computed peptide binding as a function of pH and particle size versus experimental adsorption isotherms and zeta-potentials. Representative surface models were built using characterization of the silica surfaces by TEM, SEM, BET, TGA, ζ-potential, and surface titration measurements. The results show that the recently introduced interatomic potentials (Emami et al. Chem. Mater. 2014, 26, 2647) enable computational screening of a limitless number of silica interfaces to predict the binding of drugs, cell receptors, polymers, surfactants, and gases under realistic solution conditions at the scale of 1 to 100 nm. The highly specific binding outcomes underline the significance of the surface chemistry, pH, and topography

Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity.

Recently, we identified a GTPase-activating protein for the ADP ribosylation factor family of small GTP-binding proteins that we call GIT1. This protein initially was identified as an interacting partner for the G protein-coupled receptor kinases, and its overexpression was found to affect signaling and internalization of the prototypical beta(2)-adrenergic receptor. Here, we report that GIT1 overexpression regulates internalization of numerous, but not all, G protein-coupled receptors. The specificity of the GIT1 effect is not related to the type of G protein to which a receptor couples, but rather to the endocytic route it uses. GIT1 only affects the function of G protein-coupled receptors that are internalized through the clathrin-coated pit pathway in a beta-arrestin- and dynamin-sensitive manner. Furthermore, the GIT1 effect is not limited to G protein-coupled receptors because overexpression of this protein also affects internalization of the epidermal growth factor receptor. However, constitutive agonist-independent internalization is not regulated by GIT1, because transferrin uptake is not affected by GIT1 overexpression. Thus, GIT1 is a protein involved in regulating the function of signaling receptors internalized through the clathrin pathway and can be used as a diagnostic tool for defining the endocytic pathway of a receptor

The Vacuum in Light-Cone Field Theory

This is an overview of the problem of the vacuum in light-cone field theory, stressing its close connection to other puzzles regarding light-cone quantization. I explain the sense in which the light-cone vacuum is ``trivial,'' and describe a way of setting up a quantum field theory on null planes so that it is equivalent to the usual equal-time formulation. This construction is quite helpful in resolving the puzzling aspects of the light-cone formalism. It furthermore allows the extraction of effective Hamiltonians that incorporate vacuum physics, but that act in a Hilbert space in which the vacuum state is simple. The discussion is fairly informal, and focuses mainly on the conceptual issues. [Talk presented at {\sc Orbis Scientiae 1996}, Miami Beach, FL, January 25--28, 1996. To appear in the proceedings.]Comment: 20 pages, RevTeX, 4 Postscript figures. Minor typos correcte

The potential role of cost-utility analysis in the decision to implement major system change in acute stroke services in metropolitan areas in England

BACKGROUND: The economic implications of major system change are an important component of the decision to implement health service reconfigurations. Little is known about how best to report the results of economic evaluations of major system change to inform decision-makers. Reconfiguration of acute stroke care in two metropolitan areas in England, namely London and Greater Manchester (GM), was used to analyse the economic implications of two different implementation strategies for major system change. METHODS: A decision analytic model was used to calculate difference-in-differences in costs and outcomes before and after the implementation of two major system change strategies in stroke care in London and GM. Values in the model were based on patient level data from Hospital Episode Statistics, linked mortality data from the Office of National Statistics and data from two national stroke audits. Results were presented as net monetary benefit (NMB) and using Programme Budgeting and Marginal Analysis (PBMA) to assess the costs and benefits of a hypothetical typical region in England with approximately 4000 strokes a year. RESULTS: In London, after 90 days, there were nine fewer deaths per 1000 patients compared to the rest of England (95% CI -24 to 6) at an additional cost of £770,027 per 1000 stroke patients admitted. There were two additional deaths (95% CI -19 to 23) in GM, with a total costs saving of £156,118 per 1000 patients compared to the rest of England. At a £30,000 willingness to pay the NMB was higher in London and GM than the rest of England over the same time period. The results of the PBMA suggest that a GM style reconfiguration could result in a total greater health benefit to a region. Implementation costs were £136 per patient in London and £75 in GM. CONCLUSIONS: The implementation of major system change in acute stroke care may result in a net health benefit to a region, even one functioning within a fixed budget. The choice of what model of stroke reconfiguration to implement may depend on the relative importance of clinical versus cost outcomes

Longitudinal grey and white matter changes in frontotemporal dementia and Alzheimer's disease

Behavioural variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) dementia are characterised by progressive brain atrophy. Longitudinal MRI volumetry may help to characterise ongoing structural degeneration and support the differential diagnosis of dementia subtypes. Automated, observer-independent atlas-based MRI volumetry was applied to analyse 102 MRI data sets from 15 bvFTD, 14 AD, and 10 healthy elderly control participants with consecutive scans over at least 12 months. Anatomically defined targets were chosen a priori as brain structures of interest. Groups were compared regarding volumes at clinic presentation and annual change rates. Baseline volumes, especially of grey matter compartments, were significantly reduced in bvFTD and AD patients. Grey matter volumes of the caudate and the gyrus rectus were significantly smaller in bvFTD than AD. The bvFTD group could be separated from AD on the basis of caudate volume with high accuracy (79% cases correct). Annual volume decline was markedly larger in bvFTD and AD than controls, predominantly in white matter of temporal structures. Decline in grey matter volume of the lateral orbitofrontal gyrus separated bvFTD from AD and controls. Automated longitudinal MRI volumetry discriminates bvFTD from AD. In particular, greater reduction of orbitofrontal grey matter and temporal white matter structures after 12 months is indicative of bvFTD

Light-Cone Quantization and Hadron Structure

In this talk, I review the use of the light-cone Fock expansion as a tractable and consistent description of relativistic many-body systems and bound states in quantum field theory and as a frame-independent representation of the physics of the QCD parton model. Nonperturbative methods for computing the spectrum and LC wavefunctions are briefly discussed. The light-cone Fock state representation of hadrons also describes quantum fluctuations containing intrinsic gluons, strangeness, and charm, and, in the case of nuclei, "hidden color". Fock state components of hadrons with small transverse size, such as those which dominate hard exclusive reactions, have small color dipole moments and thus diminished hadronic interactions; i.e., "color transparency". The use of light-cone Fock methods to compute loop amplitudes is illustrated by the example of the electron anomalous moment in QED. In other applications, such as the computation of the axial, magnetic, and quadrupole moments of light nuclei, the QCD relativistic Fock state description provides new insights which go well beyond the usual assumptions of traditional hadronic and nuclear physics.Comment: LaTex 36 pages, 3 figures. To obtain a copy, send e-mail to [email protected]

Impaired decisional impulsivity in pathological videogamers

Abstract Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management

A ‘quiet revolution’? The impact of Training Schools on initial teacher training partnerships

This paper discusses the impact on initial teacher training of a new policy initiative in England: the introduction of Training Schools. First, the Training School project is set in context by exploring the evolution of a partnership approach to initial teacher training in England. Ways in which Training Schools represent a break with established practice are considered together with their implications for the dominant mode of partnership led by higher education institutions (HEIs). The capacity of Training Schools to achieve their own policy objectives is examined, especially their efficacy as a strategy for managing innovation and the dissemination of innovation. The paper ends by focusing on a particular Training School project which has adopted an unusual approach to its work and enquires whether this alternative approach could offer a more profitable way forward. During the course of the paper, five different models of partnership are considered: collaborative, complementary, HEI-led, school-led and partnership within a partnership

The role of the right temporoparietal junction in perceptual conflict: detection or resolution?

The right temporoparietal junction (rTPJ) is a polysensory cortical area that plays a key role in perception and awareness. Neuroimaging evidence shows activation of rTPJ in intersensory and sensorimotor conflict situations, but it remains unclear whether this activity reflects detection or resolution of such conflicts. To address this question, we manipulated the relationship between touch and vision using the so-called mirror-box illusion. Participants' hands lay on either side of a mirror, which occluded their left hand and reflected their right hand, but created the illusion that they were looking directly at their left hand. The experimenter simultaneously touched either the middle (D3) or the ring finger (D4) of each hand. Participants judged, which finger was touched on their occluded left hand. The visual stimulus corresponding to the touch on the right hand was therefore either congruent (same finger as touch) or incongruent (different finger from touch) with the task-relevant touch on the left hand. Single-pulse transcranial magnetic stimulation (TMS) was delivered to the rTPJ immediately after touch. Accuracy in localizing the left touch was worse for D4 than for D3, particularly when visual stimulation was incongruent. However, following TMS, accuracy improved selectively for D4 in incongruent trials, suggesting that the effects of the conflicting visual information were reduced. These findings suggest a role of rTPJ in detecting, rather than resolving, intersensory conflict