Skin TLR7 triggering promotes accumulation of respiratory dendritic cells and natural killer cells.

The TLR7 agonist imiquimod has been used successfully as adjuvant for skin treatment of virus-associated warts and basal cell carcinoma. The effects of skin TLR7 triggering on respiratory leukocyte populations are unknown. In a placebo-controlled experimental animal study we have used multicolour flow cytometry to systematically analyze the modulation of respiratory leukocyte subsets after skin administration of imiquimod. Compared to placebo, skin administration of imiquimod significantly increased respiratory dendritic cells (DC) and natural killer cells, whereas total respiratory leukocyte, alveolar macrophages, classical CD4+ T helper and CD8+ T killer cell numbers were not or only moderately affected. DC subpopulation analyses revealed that elevation of respiratory DC was caused by an increase of respiratory monocytic DC and CD11b(hi) DC subsets. Lymphocyte subpopulation analyses indicated a marked elevation of respiratory natural killer cells and a significant reduction of B lymphocytes. Analysis of cytokine responses of respiratory leukocytes after stimulation with Klebsiella pneumonia indicated reduced IFN-γ and TNF-α expression and increased IL-10 and IL-12p70 production after 7 day low dose skin TLR7 triggering. Additionally, respiratory NK cytotoxic activity was increased after 7d skin TLR7 triggering. In contrast, lung histology and bronchoalveolar cell counts were not affected suggesting that skin TLR7 stimulation modulated respiratory leukocyte composition without inducing overt pulmonary inflammation. These data suggest the possibility to modulate respiratory leukocyte composition and respiratory cytokine responses against pathogens like Klebsiella pneumonia through skin administration of a clinically approved TLR7 ligand. Skin administration of synthetic TLR7 ligands may represent a novel, noninvasive means to modulate respiratory immunity

`In pursuit of the Nazi mind?' the deployment of psychoanalysis in the allied struggle against Germany

This paper discusses how psychoanalytic ideas were brought to bear in the Allied struggle against the Third Reich and explores some of the claims that were made about this endeavour. It shows how a variety of studies of Fascist psychopathology, centred on the concept of superego, were mobilized in military intelligence, post-war planning and policy recommendations for ‘denazification’. Freud's ideas were sometimes championed by particular army doctors and government planners; at other times they were combined with, or displaced by, competing, psychiatric and psychological forms of treatment and diverse studies of the Fascist ‘personality’. This is illustrated through a discussion of the treatment and interpretation of the deputy leader of the Nazi Party, Rudolf Hess, after his arrival in Britain in 1941

In vivo Neutralization of Pro-inflammatory Cytokines During Secondary Streptococcus pneumoniae Infection Post Influenza A Virus Infection

An overt pro-inflammatory immune response is a key factor contributing to lethal pneumococcal infection in an influenza pre-infected host and represents a potential target for therapeutic intervention. However, there is a paucity of knowledge about the level of contribution of individual cytokines. Based on the predictions of our previous mathematical modeling approach, the potential benefit of IFN-γ- and/or IL-6-specific antibody-mediated cytokine neutralization was explored in C57BL/6 mice infected with the influenza A/PR/8/34 strain, which were subsequently infected with the Streptococcus pneumoniae strain TIGR4 on day 7 post influenza. While single IL-6 neutralization had no effect on respiratory bacterial clearance, single IFN-γ neutralization enhanced local bacterial clearance in the lungs. Concomitant neutralization of IFN-γ and IL-6 significantly reduced the degree of pneumonia as well as bacteremia compared to the control group, indicating a positive effect for the host during secondary bacterial infection. The results of our model-driven experimental study reveal that the predicted therapeutic value of IFN-γ and IL-6 neutralization in secondary pneumococcal infection following influenza infection is tightly dependent on the experimental protocol while at the same time paving the way toward the development of effective immune therapies

Comparison of multi-year and reference year building simulations

Copyright © 2010 by SAGE PublicationsBuildings are generally modelled for compliance using reference weather years. In the UK these are the test reference year (TRY) used for energy analysis and the design summer year (DSY) used for assessing overheating in the summer. These reference years currently exist for 14 locations around the UK and consist of either a composite year compiled of the most average months from 23 years worth of observed weather data (TRY) or a single contiguous year representing a hot but non-extreme summer (DSY). In this paper, we compare simulations run using the reference years and the results obtained from simulations using the base data sets from which these reference years were chosen. We compare the posterior statistic to the reference year for several buildings examining energy use, internal temperatures, overheating and thermal comfort. We find that while the reference years allow rapid thermal modelling of building designs they are not always representative of the average energy use (TRY) exposed by modelling with many weather years. Also they do not always give an accurate indication of the internal conditions within a building and as such can give a misleading representation of the risk of overheating (DSY). Practical applications: An understanding of the limitations of the current reference years is required to allow creation of updated reference years for building simulation of future buildings. By comparing the reference years to the base data sets of historical data from which they were compiled an understanding of the benefit of multiple simulations in determining risk can be obtained

Quantum Hall induced currents and the magnetoresistance of a quantum point contact

We report an investigation of quantum Hall induced currents by simultaneous measurements of their magnetic moment and their effect on the conductance of a quantum point contact (QPC). Features in the magnetic moment and QPC resistance are correlated at Landau-level filling factors nu=1, 2 and 4, which demonstrates the common origin of the effects. Temperature and non-linear sweep rate dependences are observed to be similar for the two effects. Furthermore, features in the noise of the induced currents, caused by breakdown of the quantum Hall effect, are observed to have clear correlations between the two measurements. In contrast, there is a distinct difference in the way that the induced currents decay with time when the sweeping field halts at integer filling factor. We attribute this difference to the fact that, while both effects are sensitive to the magnitude of the induced current, the QPC resistance is also sensitive to the proximity of the current to the QPC split-gate. Although it is clearly demonstrated that induced currents affect the electrostatics of a QPC, the reverse effect, the QPC influencing the induced current, was not observed

Assessing the risk of climate change for buildings: A comparison between multi-year and probabilistic reference year simulations

Copyright © 2011 Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Building and Environment . Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Building and Environment Vol. 46 (2011), DOI: 10.1016/j.buildenv.2010.12.018Given a changing climate, there is a need to provide data for future years so that practicing engineers can investigate the impact of climate change on particular designs and examine any risk the client might be exposed to. In addition, such files are of use to building scientists in developing generic solutions to problems such as elevated internal temperatures and poor thermal comfort. With the release of the UK Climate Projections (UKCP09) [1], and the publication of a methodology for the creation of probabilistic future reference years using the UKCP09 weather generator [2], it is possible to model future building performance. However, the collapse of the distribution of possibilities inherent in the UKCP09 method into a single reference year or a small number of reference years, potentially means the loss of most of the information about the potential range of the response of the building and of the risk occupants might be subject to. In this paper we model for the first time the internal conditions and energy use of a building with all 3000 example years produced by the UKCP09 weather generator in an attempt to study the full range of response and risk. The resultant histograms and cumulative distribution functions are then used to examine whether single reference years can be used to answer questions about response and risk under a changing climate, or whether a more probabilistic approach is unavoidable

Area and individual differences in personal crime victimization incidence: The role of individual, lifestyle/routine activities and contextual predictors

This article examines how personal crime differences between areas and between individuals are predicted by area and population heterogeneity and their synergies. It draws on lifestyle/routine activities and social disorganization theories to model the number of personal victimization incidents over individuals including routine activities and area characteristics, respectively, as well as their (cross-cluster) interactions. The methodology employs multilevel or hierarchical negative binomial regression with extra binomial variation using data from the British Crime Survey and the UK Census. Personal crime rates differ substantially across areas, reflecting to a large degree the clustering of individuals with measured vulnerability factors in the same areas. Most factors suggested by theory and previous research are conducive to frequent personal victimization except the following new results. Pensioners living alone in densely populated areas face disproportionally high numbers of personal crimes. Frequent club and pub visits are associated with more personal crimes only for males and adults living with young children, respectively. Ethnic minority individuals experience fewer personal crimes than whites. The findings suggest integrating social disorganization and lifestyle theories and prioritizing resources to the most vulnerable, rather than all, residents of poor and densely populated areas to prevent personal crimes

The Identification and Synthesis of Lead Apatite Minerals Formed in Lead Water Pipes

Phosphate is added to drinking water in the UK to minimise the release of lead from lead water pipes. The phosphate encourages the formation of insoluble lead apatites on the walls of the pipe. Hydroxylpyromorphite Pb5(PO4)3OH is the lead apatite that is most often used to model lead levels in tap water; however, its presence has not been confirmed. Our aims were to identify the lead pipe apatite and synthesise it. The synthetic mineral would then be used in future solubility studies to produce better predictions of lead levels in tap water. XRD and FTIR were used to characterise the minerals on a range of lead pipes. Pyromorphite and hydroxylpyromorphite were absent and instead a range of mixed calcium lead apatites were present. For every five lead ions in the general formula Pb5(PO4)3X between one and two ions were replaced with calcium and there was evidence of substitution of by either or . Calcium lead apatites with similar unit cell dimensions to those found on lead water pipes were then synthesised. The calcium : lead ratio in these reaction mixtures was in excess of 500 : 1 and the resulting crystals were shown by TEM to be nanosized rods and flakes. The synthetic apatites that most closely resembled the unit cell dimensions of the apatites on lead water pipes were shown to be Pb3.4Ca1.3(PO4)3Cl0.03OH0.97, Pb3.6Ca1.2(PO4)3Cl0.07OH0.93, and Pb3.6Ca1.2(PO4)3Cl0.27OH0.73

Geophysical and geochemical study of geropotamos aquifer in the north-central coast of crete

The geological setting of Geropotamos aquifer on the north-central coast of Crete, Greece, is considered complex, while the local tectonic regime of the study area is characterized by two sets of faults orientated NW-SE and NE-SW. Investigation of the aquifer using the Transient ElectroMagnetic method (TEM) has resulted initially in 1D models of geoelectric structures and a final 3D geoelectrical model was constructed, depicting the zones of salination of groundwater in the aquifer. Groundwater samples were analysed and the most important chemical parameters were determined to provide an independent dataset for comparison with the TEM results, while Groundwater Quality Maps were produced. TEM and geochemical data correspond and provide verification of the TEM approach. As a result, saline intrusion is likely to occur along fractures in a fault zone through bedrock, and this work emphasises the critical role of fracture pathways in salination problems of coastal aquifers