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41.
  • Sung, Yun Ju, et al. (författare)
  • A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
  • 2019
  • Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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42.
  • Tröstl, Jasmin, et al. (författare)
  • The role of low-volatility organic compounds in initial particle growth in the atmosphere
  • 2016
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 533:7604, s. 527-531
  • Tidskriftsartikel (refereegranskat)abstract
    • About half of present-day cloud condensation nuclei originate from atmospheric nucleation, frequently appearing as a burst of new particles near midday(1). Atmospheric observations show that the growth rate of new particles often accelerates when the diameter of the particles is between one and ten nanometres(2,3). In this critical size range, new particles are most likely to be lost by coagulation with pre-existing particles(4), thereby failing to form new cloud condensation nuclei that are typically 50 to 100 nanometres across. Sulfuric acid vapour is often involved in nucleation but is too scarce to explain most subsequent growth(5,6), leaving organic vapours as the most plausible alternative, at least in the planetary boundary layer(7-10). Although recent studies(11-13) predict that low-volatility organic vapours contribute during initial growth, direct evidence has been lacking. The accelerating growth may result from increased photolytic production of condensable organic species in the afternoon(2), and the presence of a possible Kelvin (curvature) effect, which inhibits organic vapour condensation on the smallest particles (the nano-Kohler theory)(2,14), has so far remained ambiguous. Here we present experiments performed in a large chamber under atmospheric conditions that investigate the role of organic vapours in the initial growth of nucleated organic particles in the absence of inorganic acids and bases such as sulfuric acid or ammonia and amines, respectively. Using data from the same set of experiments, it has been shown(15) that organic vapours alone can drive nucleation. We focus on the growth of nucleated particles and find that the organic vapours that drive initial growth have extremely low volatilities (saturation concentration less than 10(-4.5) micrograms per cubic metre). As the particles increase in size and the Kelvin barrier falls, subsequent growth is primarily due to more abundant organic vapours of slightly higher volatility (saturation concentrations of 10(-4.5) to 10(-0.5) micrograms per cubic metre). We present a particle growth model that quantitatively reproduces our measurements. Furthermore, we implement a parameterization of the first steps of growth in a global aerosol model and find that concentrations of atmospheric cloud concentration nuclei can change substantially in response, that is, by up to 50 per cent in comparison with previously assumed growth rate parameterizations.
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43.
  • Wagner, Ryan G, 1984- (författare)
  • The Burden of Epilepsy : using population-based data to define the burden and model a cost-effective intervention for the treatment of epilepsy in rural South Africa
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Rationale Epilepsy is a common, chronic, neurological condition that disproportionately affects individuals living in low- and middle- income countries, including much of sub-Saharan Africa. Epilepsy is treatable, with the majority of individuals who take anti-epileptic drugs experiencing a reduction, or elimination, of seizures. Yet the number of individuals taking and adhering to medication in Africa is low and interventions aimed at improving treatment are lacking.Aims To define the epidemiology of convulsive epilepsy in rural South Africa in terms of incidence, mortality and disability-adjusted life years; to determine outpatient, out-of-pocket costs resulting from epilepsy treatment; to establish the level of adherence to anti-epileptic drugs amongst people with epilepsy; and, to determine whether the introduction of routine visits to people with epilepsy by community health workers is a cost-effective intervention for improving adherence to anti-epileptic drugs.Methods Nested within the Agincourt Health and Demographic Surveillance System, this work utilized a cohort of individuals diagnosed with convulsive epilepsy in 2008 to determine health care utilization and out-of-pocket costs due to care sought for epilepsy. Additionally, using blood samples from the cohort, anti-epileptic drug adherence was measured and, following the cohort, mortality rates were determined. Using these collected epidemiological parameters, disability-adjusted life years due to convulsive epilepsy were determined. Finally, combining the epidemiological and cost parameters, a community health worker intervention was modeled to determine its incremental cost-effectiveness ratio.Key Findings The burden of convulsive epilepsy is lower in rural South Africa than other parts of Africa, likely due to lower levels of known risk factors. Yet the burden, especially in terms of mortality, remains high, as does the treatment gap and health care utilization. Findings from the economic evaluation found the introduction of a community health worker to be highly cost-effective and would likely lower the burden of epilepsy in rural South Africa.Implications Epilepsy contributes to the burden of disease in rural South Africa, with high levels of mortality and a substantial treatment gap. The introduction of a community-health worker is likely to be one cost-effective, community based intervention that would lower the burden of epilepsy by improving adherence to anti-epileptic drugs. Implementing this intervention, based on these findings, is a justified and important next step.
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44.
  • Walcher, C.~J., et al. (författare)
  • 4MOST Scientific Operations
  • 2019
  • Ingår i: Messenger. - 0722-6691. ; 175, s. 12-16
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The 4MOST instrument is a multi-object spectrograph that will address Galactic and extragalactic science cases simultaneously by observing targets from a large number of different surveys within each science exposure. This parallel mode of operation and the survey nature of 4MOST require some distinct 4MOST- specific operational features within the overall operations model of ESO. The main feature is that the 4MOST Consortium will deliver, not only the instrument, but also contractual services to the user community, which is why 4MOST is also described as a facility. This white paper concentrates on information particularly useful to answering the forthcoming Call for Letters of Intent.
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45.
  • Wang, Mingyi, et al. (författare)
  • Synergistic HNO3–H2SO4–NH3 upper tropospheric particle formation
  • 2022
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 605:7910, s. 483-489
  • Tidskriftsartikel (refereegranskat)abstract
    • New particle formation in the upper free troposphere is a major global source of cloud condensation nuclei (CCN). However, the precursor vapours that drive the process are not well understood. With experiments performed under upper tropospheric conditions in the CERN CLOUD chamber, we show that nitric acid, sulfuric acid and ammonia form particles synergistically, at rates that are orders of magnitude faster than those from any two of the three components. The importance of this mechanism depends on the availability of ammonia, which was previously thought to be efficiently scavenged by cloud droplets during convection. However, surprisingly high concentrations of ammonia and ammonium nitrate have recently been observed in the upper troposphere over the Asian monsoon region. Once particles have formed, co-condensation of ammonia and abundant nitric acid alone is sufficient to drive rapid growth to CCN sizes with only trace sulfate. Moreover, our measurements show that these CCN are also highly efficient ice nucleating particles—comparable to desert dust. Our model simulations confirm that ammonia is efficiently convected aloft during the Asian monsoon, driving rapid, multi-acid HNO3–H2SO4–NH3 nucleation in the upper troposphere and producing ice nucleating particles that spread across the mid-latitude Northern Hemisphere.
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46.
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47.
  • Youahri, Yassine, et al. (författare)
  • Micro cooling of squid sensor
  • 2008
  • Ingår i: Proceedings of Micro System Workshop 2008 (MSW08) 6-7 May, Göteborg, Sweden. ; , s. S1-12
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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48.
  • Öisjöen, Fredrik, 1982, et al. (författare)
  • A new approach for bioassays based on frequency- and time-domain measurements of magnetic nanoparticles
  • 2010
  • Ingår i: Biosensors and Bioelectronics. - : Elsevier BV. - 0956-5663 .- 1873-4235. ; 25:5, s. 1008-1013
  • Tidskriftsartikel (refereegranskat)abstract
    • We demonstrate a one-step wash-free bioassay measurement system capable of tracking biochemical binding events. Our approach combines the high resolution of frequency- and high speed of time-domain measurements in a single device in combination with a fast one-step bioassay. The one-step nature of our magnetic nanoparticle (MNP) based assay reduces the time between sample extraction and quantitative results while mitigating the risks of contamination related to washing steps. Our method also enables tracking of binding events, providing the possibility of, for example, investigation of how chemical/biological environments affect the rate of a binding process or study of the action of certain drugs. We detect specific biological binding events occurring on the surfaces of fluid-suspended MNPs that modify their magnetic relaxation behavior. Herein. we extrapolate a modest sensitivity to analyte of 100 ng/ml with the present setup using our rapid one-step bioassay. More importantly, we determine the size-distributions of the MNP systems with theoretical fits to our data obtained from the two complementary measurement modalities and demonstrate quantitative agreement between them. (
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49.
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50.
  • Öisjöen, Fredrik, 1982, et al. (författare)
  • The need for stable, mono-dispersed, and biofunctional magnetic nanoparticles for one-step magnetic immunoassays
  • 2010
  • Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 200:SECTION 12, s. Art. nr. 122006-
  • Konferensbidrag (refereegranskat)abstract
    • We have developed a magnetic immunoassay system (MIA) using magnetic nanoparticle markers for biomolecule detection. We have magnetically characterized multi-core magnetic nanoparticles (MNPs) containing single-domain crystals of Fe3O4 and CoFe2O4 with our system using a high temperature superconducting quantum interference device as detector. We use a Helmholtz coil to excite the MNPs and study the AC-susceptibility. The data is fit to a model and information about the particle size distribution of the MNP system is extracted. We observe high stability of the unfunctionalized MNPs. However, our MIA measurements require stable functionalized MNPs. We have found a significant increase in hydrodynamic size of the functionalized MNP systems in the course of just a few days caused by agglomeration behaviour. Separate measurements performed at Imego AB with their AC-Susceptometer, DynoMAG, confirm these findings. Without stable, functionalized MNPs MIAs of this kind are impossible. © 2010 IOP Publishing Ltd.
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