Changes in symptoms of asthma and rhinitis by sensitization status over ten years in a cohort of young Chilean adults

BACKGROUND: We investigated the net changes in prevalence of symptoms of asthma and rhinitis over 10 years in a cohort of young by baseline sensitization status. METHODS: One thousand one hundred ninety three Chilean adults subjects aged 22-28 living in a semi-rural area of central Chile answered a lifestyle and the European Community Respiratory Health Survey (ECRHS) questionnaires. Bronchial hyper-responsiveness (BHR) and skin prick test (SPT) to eight allergens were measured at baseline in 2001. Ten years later, 772 participants completed the questionnaires again. Estimates of adjusted net changes in prevalence of symptoms by sensitization status at baseline and association between sensitization status at baseline and respiratory symptoms ten years later were assessed. RESULTS: A quarter of the participants were sensitized to at least one allergen in 2001. Prevalence of wheeze had a net change per year of -0.37 % (95 % Confidence Interval -0.71 to 0.02 %; p = 0.067). Self-reported nasal allergies in the last 12 months increased by 0.83 % per year (95 % CI 0.49 to 1.17 %; p < 0.001). Those sensitized to either cat fur (OR 1.76; CI 1.01 to 3.05), cockroach, (OR 2.09; 1.13 to 3.86) blend of grass and pollens (1.78; 95 % CI 1.08 to 2.92), or weeds (OR 1.77; 95 % CI 1.01 to 3.12) in 2001 were more likely to have wheeze in the last 12 months 10 years later. CONCLUSION: Symptoms of asthma remained stable or slightly changed over 10 years in adults, whilst rhinitis and nasal allergies greatly increased. Being sensitized to at least one allergen is a risk factor for persistent symptoms of asthma and rhinitis, but not for determining net changes of symptoms over time. The underlying causes for the contrasting trends between asthma and nasal allergy are unknow

Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

Simpson's Paradox, Lord's Paradox, and Suppression Effects are the same phenomenon – the reversal paradox

This article discusses three statistical paradoxes that pervade epidemiological research: Simpson's paradox, Lord's paradox, and suppression. These paradoxes have important implications for the interpretation of evidence from observational studies. This article uses hypothetical scenarios to illustrate how the three paradoxes are different manifestations of one phenomenon – the reversal paradox – depending on whether the outcome and explanatory variables are categorical, continuous or a combination of both; this renders the issues and remedies for any one to be similar for all three. Although the three statistical paradoxes occur in different types of variables, they share the same characteristic: the association between two variables can be reversed, diminished, or enhanced when another variable is statistically controlled for. Understanding the concepts and theory behind these paradoxes provides insights into some controversial or contradictory research findings. These paradoxes show that prior knowledge and underlying causal theory play an important role in the statistical modelling of epidemiological data, where incorrect use of statistical models might produce consistent, replicable, yet erroneous results

Hydraulic & Design Parameters in Full-Scale Constructed Wetland & Treatment Units: Six Case Studies

The efficiency of pond and constructed wetland (CW) treatment systems, is influenced by the internal hydrodynamics and mixing interactions between water and aquatic vegetation. In order to contribute to current knowledge of how emergent real vegetation affects solute mixing, and on what the shape and size effects are on the mixing characteristics, an understanding and quantification of those physical processes and interactions was evaluated. This paper presents results from tracer tests conducted during 2015-2016 in six full-scale systems in the UK under different flow regimes, operational depths, shapes and sizes, and in-/outlet configurations. The aim is to quantify the hydraulic performance and mixing characteristics of the treatment units, and to investigate the effect of size and shape on the mixing processes. Relative comparison of outlet configuration, inflow conditions, and internal features between the six different treatment units showed variations in residence times of up to a factor of 3. A key outcome of this study, demonstrated that the width is a more important dimension for the efficiency of the unit compared to the depth. Results underlined the importance of investigating hydrodynamics and physics of flow in full-size units to enhance treatment efficiency and predictions of water quality models

Interaction between Thymidylate Synthase and Its Cognate mRNA in Zebrafish Embryos

Thymidylate synthase (TS), which catalyzes the de novo synthesis of dUMP, is an important target for cancer therapy. In this report, the effects of 5-fluorouracil (5-FU) and ZD1694 on the regulation of TS gene expression were evaluated in zebrafish embryos. Our results revealed that the expression of TS was increased by about six-fold when embryos were treated with 1.0 µM 5-FU and there was a greater than 10-fold increase in the TS protein level after treatment with 0.4 µM ZD1694. Northern blot analysis confirmed that expression of TS mRNA was identical in treated or untreated embryos. Gel shift and immunoprecipitation assays revealed that zebrafish TS was specifically bound with its cognate mRNA in vitro and in vivo. We identified a 20 nt RNA sequence, TS:N20, localized to the 5′-UTR of TS mRNA, which corresponded to nt 13–32; TS:N20 bound to the TS protein with an affinity similar to that of the full-length TS mRNA. The MFold program predicted that TS:N20 formed a stable stem-loop structure similar to that of the cis-acting element found in human TS mRNA. Variant RNAs with either a deletion or mutation in the core motif of TS:N20 were unable to bind to the TS protein. In vitro translation experiments, using the rabbit lysate system, confirmed that zebrafish TS mRNA translation was significantly repressed when an excess amount of TS protein was included in the system. Additionally, a TS stability experiment confirmed that treatment of zebrafish embryos with 5-FU could increase the TS stability significantly, and the half life of TS protein was about 2.7 times longer than in untreated embryos. Our study revealed a structural requirement for the interaction of TS RNA with TS protein. These findings also demonstrated that the increase in TS protein induced by 5-FU occurs at the post-transcriptional level and that increased stability and translation efficiency both contributed to the increase in TS protein levels induced by TS inhibitors

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Inclusion of diverse populations in genomic research and health services: Genomix workshop report

Clinical genetic services and genomic research are rapidly developing but, historically, those with the greatest need are the least to benefit from these advances. This encompasses low-income communities, including those from ethnic minority and indigenous backgrounds. The “Genomix” workshop at the European Society of Human Genetics (ESHG) 2016 conference offered the opportunity to consider possible solutions for these disparities from the experiences of researchers and genetic healthcare practitioners working with underserved communities in the USA, UK and Australia. Evident from the workshop and corresponding literature is that a multi-faceted approach to engaging communities is essential. This needs to be complemented by redesigning healthcare systems that improves access and raises awareness of the needs of these communities. At a more strategic level, institutions involved in funding research, commissioning and redesigning genetic health services also need to be adequately represented by underserved populations with intrinsic mechanisms to disseminate good practice and monitor participation. Further, as genomic medicine is mainstreamed, educational programmes developed for clinicians should incorporate approaches to alleviate disparities in accessing genetic services and improving study participation

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal