Confocal Fluorescence Microscopy of the Morphology and Composition of Interstitial Fluids in Freezing Electrolyte Solutions

Ice rheology, the integrity of polar ice core records, and ice−atmosphere interactions are among the phenomena controlled by the morphology and composition of interstitial fluids threading polycrystalline ice. Herein, we investigate how ionic impurities affect such features via time-resolved confocal fluorescence microscopy of freezing electrolyte solutions doped with a pH probe. We find that the 10 μM probe accumulates into 12 μm thick glassy channels in frozen water, but it is incorporated into randomly distributed <1 μm diameter inclusions in freezing 1 mM NaCl. We infer that morphology is largely determined by the dynamic instabilities generated upon advancing ice by the rejected solute, rather than by thermodynamics. The protracted alkalinization of the fluid inclusions reveals that the excess negative charge generated by the preferential incorporation of Cl^− over Na^+ in ice is neutralized by the seepage of the OH^− slowly produced via H_2O → H^+ + OH^− thermal dissociation

Association between Serum 25-Hydroxy Vitamin D Levels and the Prevalence of Adult-Onset Asthma

The major circulating metabolite of vitamin D (25(OH)D) has been implicated in the pathogenesis for atopic dermatitis, asthma and other allergic diseases due to downstream immunomodulatory effects. However, a consistent association between 25(OH)D and asthma during adulthood has yet to be found in observational studies. We aimed to test the association between 25(OH)D and asthma during adulthood and hypothesised that this association would be stronger in non-atopic participants. Using information collected on the participants of the 1958 birth cohort, we developed a novel measure of atopic status using total and specific IgE values and reported history of eczema and allergic rhinitis. We designed a nested case-control analysis, stratified by atopic status, and using logistic regression models investigated the association between 25(OH)D measured at age 46 years with the prevalence of asthma and wheezy bronchitis at age 50 years, excluding participants who reported ever having asthma or wheezy bronchitis before the age of 42. In the fully adjusted models, a 10 nmol/L increase in serum 25(OH)D prevalence had a significant association with asthma (aOR 0.94; 95% CI 0.88&ndash;1.00). There was some evidence of an atopic dependent trend in the association between 25(OH)D levels and asthma. Further analytical work on the operationalisation of atopy status would prove useful to uncover whether there is a role for 25(OH)D and other risk factors for asthma

P4_3 Shrinking the Earth

This article investigates the energy requirements to compress the Earth to within 1 km. This was done using a model assuming the compression to be elastic, and another model estimating the energy to overcome the Coulomb repulsion between the constituent protons. The energies found were 3.1x1032 J and 8.3x1038 J for each model respectively. It was also shown that to compress the Earth to within 1125 km you would have to overcome electron and neutron degeneracy pressure, and if compressed to a radius of 9 mm, the Earth would be a black hole.

P4_2 Tidal forces in the solar system

This article investigates the tidal accelerations exerted by planets on orbiting moons. The tidal acceleration was calculated, in terms of the acceleration due to gravity at the planet's surface, for several planetary systems in the solar system. A plot was created which showed that for most planetary systems, the tidal acceleration varied inversely as the cube of the semi-major axis, as theory predicted for the Earth and Moon

Therapeutic Targeting of IRFs: Pathway-Dependence or Structure-Based?

The interferon regulatory factors (IRFs) are a family of master transcription factors that regulate pathogen-induced innate and acquired immune responses. Aberration(s) in IRF signaling pathways due to infection, genetic predisposition and/or mutation, which can lead to increased expression of type I interferon (IFN) genes, IFN-stimulated genes (ISGs), and other pro-inflammatory cytokines/chemokines, has been linked to the development of numerous diseases, including (but not limited to) autoimmune and cancer. What is currently lacking in the field is an understanding of how best to therapeutically target these transcription factors. Many IRFs are regulated by post-translational modifications downstream of pattern recognition receptors (PRRs) and some of these modifications lead to activation or inhibition. We and others have been able to utilize structural features of the IRFs in order to generate dominant negative mutants that inhibit function. Here, we will review potential therapeutic strategies for targeting all IRFs by using IRF5 as a candidate targeting molecule

Ambient particulate matter and biomass burning:an ecological time series study of respiratory and cardiovascular hospital visits in northern Thailand

Background Exposure to particulate matter (PM) emitted from biomass burning is an increasing concern, particularly in Southeast Asia. It is not yet clear how the source of PM influences the risk of an adverse health outcome. The objective of this study was to quantify and compare health risks of PM from biomass burning and non-biomass burning sources in northern Thailand. Methods We collected ambient air pollutant data (PM with a diameter of < 10 μm [PM10], PM2.5, Carbon Monoxide [CO], Ozone [O3], and Nitrogen Dioxide [NO2]) from ground-based monitors and daily outpatient hospital visits in Thailand during 2014–2017. Outpatient data included chronic lower respiratory disease (CLRD), ischaemic heart disease (IHD), and cerebrovascular disease (CBVD). We performed an ecological time series analysis to evaluate the association between daily air pollutants and outpatient visits. We used the 90th and 95th percentiles of PM10 concentrations to determine days of exposure to PM predominantly from biomass burning. Results There was significant intra annual variation in PM10 levels, with the highest concentrations occurring during March, coinciding with peak biomass burning. Incidence Rate Ratios (IRRs) between daily PM10 and outpatient visits were elevated most on the same day as exposure for CLRD = 1.020 (95% CI: 1.012 to 1.028) and CBVD = 1.020 (95% CI: 1.004 to 1.035), with no association with IHD = 0.994 (95% CI: 0.974 to 1.014). Adjusting for CO tended to increase effect estimates. We did not find evidence of an exposure response relationship with levels of PM10 on days of biomass burning. Conclusions We found same-day exposures of PM10 to be associated with certain respiratory and cardiovascular outpatient visits. We advise implementing measures to reduce population exposures to PM wherever possible, and to improve understanding of health effects associated with burning specific types of biomass in areas where such large-scale activities occur.This study was funded by the Medical Research Council (MRC) (MR/R006210/1) and the Thailand Research Fund (TRF) (RDG603009)

Occupational cancer in Britain: Exposure assessment methodology

To estimate the current occupational cancer burden due to past exposures in Britain, estimates of the number of exposed workers at different levels are required, as well as risk estimates of cancer due to the exposures. This paper describes the methods and results for estimating the historical exposures. All occupational carcinogens or exposure circumstances classified by the International Agency for Research on Cancer as definite or probable human carcinogens and potentially to be found in British workplaces over the past 20–40 years were included in this study. Estimates of the number of people exposed by industrial sector were based predominantly on two sources of data, the CARcinogen EXposure (CAREX) database and the UK Labour Force Survey. Where possible, multiple and overlapping exposures were taken into account. Dose–response risk estimates were generally not available in the epidemiological literature for the cancer–exposure pairs in this study, and none of the sources available for obtaining the numbers exposed provided data by different levels of exposure. Industrial sectors were therefore assigned using expert judgement to ‘higher'- and ‘lower'-exposure groups based on the similarity of exposure to the population in the key epidemiological studies from which risk estimates had been selected. Estimates of historical exposure prevalence were obtained for 41 carcinogens or occupational circumstances. These include exposures to chemicals and metals, combustion products, other mixtures or groups of chemicals, mineral and biological dusts, physical agents and work patterns, as well as occupations and industries that have been associated with increased risk of cancer, but for which the causative agents are unknown. There were more than half a million workers exposed to each of six carcinogens (radon, solar radiation, crystalline silica, mineral oils, non-arsenical insecticides and 2,3,7,8-tetrachlorodibenzo-p-dioxin); other agents to which a large number of workers are exposed included benzene, diesel engine exhaust and environmental tobacco smoke. The study has highlighted several industrial sectors with large proportions of workers potentially exposed to multiple carcinogens. The relevant available data have been used to generate estimates of the prevalence of past exposure to occupational carcinogens to enable the occupational cancer burden in Britain to be estimated. These data are considered adequate for the present purpose, but new data on the prevalence and intensity of current occupational exposure to carcinogens should be collected to ensure that future policy decisions be based on reliable evidence

Evaluating Testing Strategies for Identifying Youths With HIV Infection and Linking Youths to Biomedical and Other Prevention Services

Importance: Most human immunodeficiency virus (HIV)-infected youths are unaware of their serostatus (approximately 60%) and therefore not linked to HIV medical or prevention services. The need to identify promising and scalable approaches to promote uptake of HIV testing among youths at risk is critical. Objective: To evaluate a multisite HIV testing program designed to encourage localized HIV testing programs focused on self-identified sexual minority males and to link youths to appropriate prevention services after receipt of their test results. Design, Setting, and Participants: Testing strategies were evaluated using an observational design during a 9-month period (June 1, 2015, through February 28, 2016). Testing strategies were implemented by 12 adolescent medicine HIV primary care programs and included targeted testing, universal testing, or a combination. Data were collected from local youth at high risk of HIV infection and, specifically, sexual minority males of color. Main Outcomes and Measures: Proportion of sexual minority males and sexual minority males of color tested, proportion of previously undiagnosed HIV-positive youths identified, and rates of linkage to prevention services. Results: A total of 3301 youths underwent HIV testing. Overall, 35 (3.6%) of those who underwent universal testing in primary care clinical settings, such as emergency departments and community health centers, were sexual minority males (35 [3.6%] were males of color) compared with 236 (46.7%) (201 [39.8%] were males of color) who were tested through targeted testing and 693 (37.8%) (503 [27.4%] were males of color) through combination efforts. Identification of new HIV-positive cases varied by strategy: 1 (0.1%) via universal testing, 39 (2.1%) through combination testing, and 16 (3.2%) through targeted testing. However, when targeted tests were separated from universal testing results for sites using a combined strategy, the rate of newly identified HIV-positive cases identified through universal testing decreased to 1 (0.1%). Rates of new HIV-positive cases identified through targeted testing increased to 49 (6.3%). Youths who tested through targeted testing (416 [85.1%]) were more likely to link successfully to local HIV prevention services, including preexposure prophylaxis, compared with those who underwent universal testing (328 [34.1%]). Conclusions and Relevance: The findings suggest that community-based targeted approaches to HIV testing are more effective than universal screening for reaching young sexual minority males (especially males of color), identifying previously undiagnosed HIV-positive youths, and linking HIV-negative youths to relevant prevention services. Targeted, community-based HIV testing strategies hold promise as a scalable and effective means to identify high-risk youths who are unaware of their HIV status