PO and ID BCG vaccination in humans induce distinct mucosal and systemic immune responses and CD4(+) T cell transcriptomal molecular signatures.

Protective efficacy of Bacillus Calmette-Guérin (BCG) may be affected by the methods and routes of vaccine administration. We have studied the safety and immunogenicity of oral (PO) and/or intradermal (ID) administration of BCG in healthy human subjects. No major safety concerns were detected in the 68 healthy adults vaccinated with PO and/or ID BCG. Although both PO and ID BCG could induce systemic Th1 responses capable of IFN-γ production, ID BCG more strongly induced systemic Th1 responses. In contrast, stronger mucosal responses (TB-specific secretory IgA and bronchoalveolar lavage T cells) were induced by PO BCG vaccination. To generate preliminary data comparing the early gene signatures induced by mucosal and systemic BCG vaccination, CD4(+) memory T cells were isolated from subsets of BCG vaccinated subjects pre- (Day 0) and post-vaccination (Days 7 and 56), rested or stimulated with BCG infected dendritic cells, and then studied by Illumina BeadArray transcriptomal analysis. Notably, distinct gene expression profiles were identified both on Day 7 and Day 56 comparing the PO and ID BCG vaccinated groups by GSEA analysis. Future correlation analyses between specific gene expression patterns and distinct mucosal and systemic immune responses induced will be highly informative for TB vaccine development.Mucosal Immunology advance online publication 30 August 2017; doi:10.1038/mi.2017.67

Isomonodromic deformations of connections with singularities of parahoric formal type

In previous work, the authors have developed a geometric theory of fundamental strata to study connections on the projective line with irregular singularities of parahoric formal type. In this paper, the moduli space of connections that contain regular fundamental strata with fixed combinatorics at each singular point is constructed as a smooth Poisson reduction. The authors then explicitly compute the isomonodromy equations as an integrable system. This result generalizes work of Jimbo, Miwa, and Ueno to connections whose singularities have parahoric formal type.Comment: 32 pages. One of the main theorems (Theorem 5.1) has been significantly strengthened. It now states that the isomonodromy equations give rise to an integrable system on the moduli space of framed connections with fixed combinatorics instead of only on a principal GL_n bundle over this space. Sections 5 and 6 have been substantially rewritte

Measuring the vertical age structure of the Galactic disc using asteroseismology and SAGA

The existence of a vertical age gradient in the Milky Way disc has been indirectly known for long. Here, we measure it directly for the first time with seismic ages, using red giants observed by Kepler. We use Stroemgren photometry to gauge the selection function of asteroseismic targets, and derive colour and magnitude limits where giants with measured oscillations are representative of the underlying population in the field. Limits in the 2MASS system are also derived. We lay out a method to assess and correct for target selection effects independent of Galaxy models. We find that low mass, i.e. old red giants dominate at increasing Galactic heights, whereas closer to the Galactic plane they exhibit a wide range of ages and metallicities. Parametrizing this as a vertical gradient returns approximately 4 Gyr/kpc for the disc we probe, although with a large dispersion of ages at all heights. The ages of stars show a smooth distribution over the last 10 Gyr, consistent with a mostly quiescent evolution for the Milky Way disc since a redshift of about 2. We also find a flat age-metallicity relation for disc stars. Finally, we show how to use secondary clump stars to estimate the present-day intrinsic metallicity spread, and suggest using their number count as a new proxy for tracing the ageing of the disc. This work highlights the power of asteroseismology for Galactic studies; however, we also emphasize the need for better constraints on stellar mass-loss, which is a major source of systematic age uncertainties in red giant stars.Comment: MNRAS, accepted. SAGA website and data at http://www.mso.anu.edu.au/saga/data_access.htm

Gamma-ray bursts and terrestrial planetary atmospheres

We describe results of modeling the effects on Earth-like planets of long-duration gamma-ray bursts (GRBs) within a few kiloparsecs. A primary effect is generation of nitrogen oxide compounds which deplete ozone. Ozone depletion leads to an increase in solar UVB radiation at the surface, enhancing DNA damage, particularly in marine microorganisms such as phytoplankton. In addition, we expect increased atmospheric opacity due to buildup of nitrogen dioxide produced by the burst and enhanced precipitation of nitric acid. We review here previous work on this subject and discuss recent developments, including further discussion of our estimates of the rates of impacting GRBs and the possible role of short-duration bursts.Comment: 12 pages including 5 figures (4 in color). Added discussion of GRB rates and biological effects. Accepted for publication in New Journal of Physics, for special issue "Focus on Gamma-Ray Bursts

The most creative organization in the world? The BBC, 'creativity' and managerial style

The managerial styles of two BBC directors-general, John Birt and Greg Dyke, have often been contrasted but not so far analysed from the perspective of their different views of 'creative management'. This article first addresses the orthodox reading of 'Birtism'; second, it locates Dyke's 'creative' turn in the wider context of fashionable neo-management theory and UK government creative industries policy; third, it details Dyke's drive to change the BBC's culture; and finally, it concludes with some reflections on the uncertainties inherent in managing a creative organisation

Role of diet in type 2 diabetes incidence: umbrella review of meta-analyses of prospective observational studies

OBJECTIVE: To summarise the evidence of associations between dietary factors and incidence of type 2 diabetes and to evaluate the strength and validity of these associations. DESIGN: Umbrella review of systematic reviews with meta-analyses of prospective observational studies. DATA SOURCES: PubMed, Web of Science, and Embase, searched up to August 2018. ELIGIBILITY CRITERIA: Systematic reviews with meta-analyses reporting summary risk estimates for the associations between incidence of type 2 diabetes and dietary behaviours or diet quality indices, food groups, foods, beverages, alcoholic beverages, macronutrients, and micronutrients. RESULTS: 53 publications were included, with 153 adjusted summary hazard ratios on dietary behaviours or diet quality indices (n=12), food groups and foods (n=56), beverages (n=10), alcoholic beverages (n=12), macronutrients (n=32), and micronutrients (n=31), regarding incidence of type 2 diabetes. Methodological quality was high for 75% (n=115) of meta-analyses, moderate for 23% (n=35), and low for 2% (n=3). Quality of evidence was rated high for an inverse association for type 2 diabetes incidence with increased intake of whole grains (for an increment of 30 g/day, adjusted summary hazard ratio 0.87 (95% confidence interval 0.82 to 0.93)) and cereal fibre (for an increment of 10 g/day, 0.75 (0.65 to 0.86)), as well as for moderate intake of total alcohol (for an intake of 12-24 g/day v no consumption, 0.75 (0.67 to 0.83)). Quality of evidence was also high for the association for increased incidence of type 2 diabetes with higher intake of red meat (for an increment of 100 g/day, 1.17 (1.08 to 1.26)), processed meat (for an increment of 50 g/day, 1.37 (1.22 to 1.54)), bacon (per two slices/day, 2.07 (1.40 to 3.05)), and sugar sweetened beverages (for an increase of one serving/day, 1.26 (1.11 to 1.43)). CONCLUSIONS: Overall, the association between dietary factors and type 2 diabetes has been extensively studied, but few of the associations were graded as high quality of evidence. Further factors are likely to be important in type 2 diabetes prevention; thus, more well conducted research, with more detailed assessment of diet, is needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018088106

Doping-Induced Electron Transfer at Organic/Oxide Interfaces: Direct Evidence from Infrared Spectroscopy

Charge transfer at organic/inorganic interfaces critically influences the properties of molecular adlayers. Although for metals such charge transfers are well documented by experimental and theoretical results, in the case of semiconductors, clear and direct evidence for a transfer of electrons or holes from oxides with their typically high ionization energy is missing. Here, we present data from infrared reflection−absorption spectroscopy demonstrating that despite a high ionization energy, electrons are transferred from ZnO into a prototype strong molecular electron acceptor, hexafluoro-tetracyano-naphthoquinodimethane (F$_{6}$-TCNNQ). Because there are no previous studies of this type, the interpretation of the pronounced vibrational red shifts observed in the experiment was aided by a thorough theoretical analysis using density functional theory. The calculations reveal that two mechanisms govern the pronounced vibrational band shifts of the adsorbed molecules: electron transfer into unoccupied molecular levels of the organic acceptor and also the bonding between the surface Zn atoms and the peripheral cyano groups. These combined experimental data and the theoretical analysis provide the so-far missing evidence of interfacial electron transfer from high ionization energy inorganic semiconductors to molecular acceptors and indicates that n-doping of ZnO plays a crucial role

Beyond the Refugee Crisis how the UK news media represent asylum seekers across national boundaries

Migration is one of the most pressing, divisive issues in global politics today, and media play a crucial role in how communities understand and respond. This study examines how UK newspapers (n = 974) and popular news websites (n = 1044) reported on asylum seekers throughout 2017. It contributes to previous literature in two important ways. First, by examining the ‘new normal’ of daily news coverage in the wake of the 2015 ‘refugee crisis’ in Europe. Second, by looking at how asylum seekers from different regions are represented. The content analysis finds significant variations in how asylum seekers are reported, including terminology use and topics they are associated with. The paper also identifies important commonalities in how all asylum seekers are represented - most notably, the dominance of political elites as sources across all media content. It argues that Entman’s ‘cascade network model’ can help to explain this, with elites in one country able to influence transnational reports