23 results on '"Way MJ"'
Search Results
2. Heterozygote Träger der Alpha1-Antitrypsin-Variante PiZ neigen zur Entwicklung einer Leberfibrose
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Strnad, P, additional, Buch, S, additional, Hamesch, K, additional, Gutberlet, M, additional, Rosendahl, J, additional, Fischer, J, additional, Nischalke, HD, additional, Janciauskiene, S, additional, Mandorfer, M, additional, Trauner, M, additional, McQuillin, A, additional, Way, MJ, additional, Reichert, M, additional, Lammert, F, additional, Sipos, B, additional, Schafmayer, C, additional, Aigner, E, additional, Datz, C, additional, Stickel, F, additional, Morgan, MY, additional, Hampe, J, additional, Berg, T, additional, and Trautwein, C, additional
- Published
- 2017
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3. PWE-033 Promoter Region Variations in The Glutaminase Gene as A Risk Factor for The Development Hepatic Encephalopathy in Patients with Cirrhosis: Abstract PWE-033 Table 1
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Goh, ET, primary, Way, MJ, additional, Atkinson, SR, additional, McQuillin, A, additional, and Morgan, MY, additional
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- 2016
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4. Supplementary online material for article, ? Structure in the 3D Galaxy Distribution. II. Voids and Watersheds of Local Maxima and Minima?
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Way, MJ, primary, Gazis, PR, additional, and Scargle, Jeffry, additional
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- 2015
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5. Deriving new mixing ratios for Venus atmospheric gases using data from the Pioneer Venus Large Probe Neutral Mass Spectrometer.
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Mogul R, Avice G, Limaye SS, and Way MJ
- Abstract
We present the first published method to convert data obtained by the Pioneer Venus Large Probe Neutral Mass Spectrometer (LNMS) into units of mixing ratio (ppm) and volume percent (v%) against CO
2 and N2 , the dominant Venus atmospheric gases, including conversion to density (kg m-3 ). These unit conversions are key to unlocking the untapped potential of the data, which represents a significant challenge given the scant calibration data in the literature. Herein, we show that our data treatments and conversions yield mixing ratios and volume percent values for H2 O, N2 , and SO2 that are within error to those reported for the gas chromatograph (LGC) on the Pioneer Venus Large Probe (PVLP). For the noble gases, we developed strategies to correct for instrument biases by treating the data as a relative scale and using PVLP and Venera-based measurements as calibration points. Together, these methods, conversions, calibrations, and comparisons afford novel unit conversions for the LNMS data and yield unified measures for Venus' atmosphere from the LNMS and LGC on the PVLP.•Conversion into mixing ratio (ppm), volume percent (v%), and density (kg m-3 ).•Mixing ratios are expressed against CO2 and N2 .•LNMS and LGC measurements on the PVLP are consistent., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper., (© 2023 The Authors.)- Published
- 2023
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6. Synergies Between Venus & Exoplanetary Observations: Venus and Its Extrasolar Siblings.
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Way MJ, Ostberg C, Foley BJ, Gillmann C, Höning D, Lammer H, O'Rourke J, Persson M, Plesa AC, Salvador A, Scherf M, and Weller M
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Here we examine how our knowledge of present day Venus can inform terrestrial exoplanetary science and how exoplanetary science can inform our study of Venus. In a superficial way the contrasts in knowledge appear stark. We have been looking at Venus for millennia and studying it via telescopic observations for centuries. Spacecraft observations began with Mariner 2 in 1962 when we confirmed that Venus was a hothouse planet, rather than the tropical paradise science fiction pictured. As long as our level of exploration and understanding of Venus remains far below that of Mars, major questions will endure. On the other hand, exoplanetary science has grown leaps and bounds since the discovery of Pegasus 51b in 1995, not too long after the golden years of Venus spacecraft missions came to an end with the Magellan Mission in 1994. Multi-million to billion dollar/euro exoplanet focused spacecraft missions such as JWST, and its successors will be flown in the coming decades. At the same time, excitement about Venus exploration is blooming again with a number of confirmed and proposed missions in the coming decades from India, Russia, Japan, the European Space Agency (ESA) and the National Aeronautics and Space Administration (NASA). Here we review what is known and what we may discover tomorrow in complementary studies of Venus and its exoplanetary cousins., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s) 2023.)
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- 2023
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7. Adapting Agriculture to Climate Change: A Synopsis of Coordinated National Crop Wild Relative Seed Collecting Programs across Five Continents.
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Eastwood RJ, Tambam BB, Aboagye LM, Akparov ZI, Aladele SE, Allen R, Amri A, Anglin NL, Araya R, Arrieta-Espinoza G, Asgerov A, Awang K, Awas T, Barata AM, Boateng SK, Magos Brehm J, Breidy J, Breman E, Brenes Angulo A, Burle ML, Castañeda-Álvarez NP, Casimiro P, Chaves NF, Clemente AS, Cockel CP, Davey A, De la Rosa L, Debouck DG, Dempewolf H, Dokmak H, Ellis D, Faruk A, Freitas C, Galstyan S, García RM, Ghimire KH, Guarino L, Harker R, Hope R, Humphries AW, Jamora N, Jatoi SA, Khutsishvili M, Kikodze D, Kyratzis AC, León-Lobos P, Liu U, Mainali RP, Mammadov AT, Manrique-Carpintero NC, Manzella D, Mat Ali MS, Medeiros MB, Mérida Guzmán MA, Mikatadze-Pantsulaia T, Mohamed ETI, Monteros-Altamirano Á, Morales A, Müller JV, Mulumba JW, Nersesyan A, Nóbrega H, Nyamongo DO, Obreza M, Okere AU, Orsenigo S, Ortega-Klose F, Papikyan A, Pearce TR, Pinheiro de Carvalho MAA, Prohens J, Rossi G, Salas A, Singh Shrestha D, Siddiqui SU, Smith PP, Sotomayor DA, Tacán M, Tapia C, Toledo Á, Toll J, Vu DT, Vu TD, Way MJ, Yazbek M, Zorrilla C, and Kilian B
- Abstract
The Adapting Agriculture to Climate Change Project set out to improve the diversity, quantity, and accessibility of germplasm collections of crop wild relatives (CWR). Between 2013 and 2018, partners in 25 countries, heirs to the globetrotting legacy of Nikolai Vavilov, undertook seed collecting expeditions targeting CWR of 28 crops of global significance for agriculture. Here, we describe the implementation of the 25 national collecting programs and present the key results. A total of 4587 unique seed samples from at least 355 CWR taxa were collected, conserved ex situ, safety duplicated in national and international genebanks, and made available through the Multilateral System (MLS) of the International Treaty on Plant Genetic Resources for Food and Agriculture (Plant Treaty). Collections of CWR were made for all 28 targeted crops. Potato and eggplant were the most collected genepools, although the greatest number of primary genepool collections were made for rice. Overall, alfalfa, Bambara groundnut, grass pea and wheat were the genepools for which targets were best achieved. Several of the newly collected samples have already been used in pre-breeding programs to adapt crops to future challenges.
- Published
- 2022
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8. Circumpolar ocean stability on Mars 3 Gy ago.
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Schmidt F, Way MJ, Costard F, Bouley S, Séjourné A, and Aleinov I
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What was the nature of the Late Hesperian climate, warm and wet or cold and dry? Formulated this way the question leads to an apparent paradox since both options seem implausible. A warm and wet climate would have produced extensive fluvial erosion but few valley networks have been observed at the age of the Late Hesperian. A too cold climate would have kept any northern ocean frozen most of the time. A moderate cold climate would have transferred the water from the ocean to the land in the form of snow and ice. But this would prevent tsunami formation, for which there is some evidence. Here, we provide insights from numerical climate simulations in agreement with surface geological features to demonstrate that the Martian climate could have been both cold and wet. Using an advanced general circulation model (GCM), we demonstrate that an ocean can be stable, even if the Martian mean surface temperature is lower than 0 °C. Rainfall is moderate near the shorelines and in the ocean. The southern plateau is mostly covered by ice with a mean temperature below 0 °C and a glacier return flow back to the ocean. This climate is achieved with a 1-bar CO
2 -dominated atmosphere with 10% H2 Under this scenario of 3 Ga, the geologic evidence of a shoreline and tsunami deposits along the ocean/land dichotomy are compatible with ice sheets and glacial valleys in the southern highlands., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)- Published
- 2022
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9. Venus, an Astrobiology Target.
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Limaye SS, Mogul R, Baines KH, Bullock MA, Cockell C, Cutts JA, Gentry DM, Grinspoon DH, Head JW, Jessup KL, Kompanichenko V, Lee YJ, Mathies R, Milojevic T, Pertzborn RA, Rothschild L, Sasaki S, Schulze-Makuch D, Smith DJ, and Way MJ
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- Earth, Planet, Exobiology, Planets, Extraterrestrial Environment, Venus
- Abstract
We present a case for the exploration of Venus as an astrobiology target-(1) investigations focused on the likelihood that liquid water existed on the surface in the past, leading to the potential for the origin and evolution of life, (2) investigations into the potential for habitable zones within Venus' present-day clouds and Venus-like exo atmospheres, (3) theoretical investigations into how active aerobiology may impact the radiative energy balance of Venus' clouds and Venus-like atmospheres, and (4) application of these investigative approaches toward better understanding the atmospheric dynamics and habitability of exoplanets. The proximity of Venus to Earth, guidance for exoplanet habitability investigations, and access to the potential cloud habitable layer and surface for prolonged in situ extended measurements together make the planet a very attractive target for near term astrobiological exploration.
- Published
- 2021
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10. Venus' Mass Spectra Show Signs of Disequilibria in the Middle Clouds.
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Mogul R, Limaye SS, Way MJ, and Cordova JA
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We present a re-examination of mass spectral data obtained from the Pioneer Venus Large Probe Neutral Mass Spectrometer. Our interpretations of differing trace chemical species are suggestive of redox disequilibria in Venus' middle clouds. Assignments to the data (at 51.3 km) include phosphine, hydrogen sulfide, nitrous acid, nitric acid, carbon monoxide, hydrochloric acid, hydrogen cyanide, ethane, and potentially ammonia, chlorous acid, and several tentative P
x Oy species. All parent ions were predicated upon assignment of corresponding fragmentation products, isotopologues, and atomic species. The data reveal parent ions at varying oxidation states, implying the presence of reducing power in the clouds, and illuminating the potential for chemistries yet to be discovered. When considering the hypothetical habitability of Venus' clouds, the assignments reveal a potential signature of anaerobic phosphorus metabolism (phosphine), an electron donor for anoxygenic photosynthesis (nitrite), and major constituents of the nitrogen cycle (nitrate, nitrite, ammonia, and N2 )., Competing Interests: All authors declare that there are no conflict of interests., (© 2021. The Authors.)- Published
- 2021
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11. Albedos, Equilibrium Temperatures, and Surface Temperatures of Habitable Planets.
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Del Genio AD, Kiang NY, Way MJ, Amundsen DS, Sohl LE, Fujii Y, Chandler M, Aleinov I, Colose CM, Guzewich SD, and Kelley M
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The potential habitability of known exoplanets is often categorized by a nominal equilibrium temperature assuming a Bond albedo of either ∼0.3, similar to Earth, or 0. As an indicator of habitability, this leaves much to be desired, because albedos of other planets can be very different, and because surface temperature exceeds equilibrium temperature due to the atmospheric greenhouse effect. We use an ensemble of general circulation model simulations to show that for a range of habitable planets, much of the variability of Bond albedo, equilibrium temperature and even surface temperature can be predicted with useful accuracy from incident stellar flux and stellar temperature, two known parameters for every confirmed exoplanet. Earth's Bond albedo is near the minimum possible for habitable planets orbiting G stars, because of increasing contributions from clouds and sea ice/snow at higher and lower instellations, respectively. For habitable M star planets, Bond albedo is usually lower than Earth's because of near-IR H
2 O absorption, except at high instellation where clouds are important. We apply relationships derived from this behavior to several known exoplanets to derive zeroth-order estimates of their potential habitability. More expansive multivariate statistical models that include currently non-observable parameters show that greenhouse gas variations produce significant variance in albedo and surface temperature, while increasing length of day and land fraction decrease surface temperature; insights for other parameters are limited by our sampling. We discuss how emerging information from global climate models might resolve some degeneracies and help focus scarce observing resources on the most promising planets.- Published
- 2019
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12. Heterozygous carriage of the alpha1-antitrypsin Pi*Z variant increases the risk to develop liver cirrhosis.
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Strnad P, Buch S, Hamesch K, Fischer J, Rosendahl J, Schmelz R, Brueckner S, Brosch M, Heimes CV, Woditsch V, Scholten D, Nischalke HD, Janciauskiene S, Mandorfer M, Trauner M, Way MJ, McQuillin A, Reichert MC, Krawczyk M, Casper M, Lammert F, Braun F, von Schönfels W, Hinz S, Burmeister G, Hellerbrand C, Teufel A, Feldman A, Schattenberg JM, Bantel H, Pathil A, Demir M, Kluwe J, Boettler T, Ridinger M, Wodarz N, Soyka M, Rietschel M, Kiefer F, Weber T, Marhenke S, Vogel A, Hinrichsen H, Canbay A, Schlattjan M, Sosnowsky K, Sarrazin C, von Felden J, Geier A, Deltenre P, Sipos B, Schafmayer C, Nothnagel M, Aigner E, Datz C, Stickel F, Morgan MY, Hampe J, Berg T, and Trautwein C
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- Age Distribution, Austria, Biopsy, Needle, Case-Control Studies, Confidence Intervals, Female, Genetic Carrier Screening, Genetic Variation, Germany, Humans, Immunohistochemistry, Incidence, Liver Cirrhosis, Alcoholic epidemiology, Liver Cirrhosis, Alcoholic pathology, Male, Non-alcoholic Fatty Liver Disease epidemiology, Non-alcoholic Fatty Liver Disease genetics, Non-alcoholic Fatty Liver Disease pathology, Odds Ratio, Polymorphism, Single Nucleotide, Prognosis, Risk Assessment, Sex Distribution, Genetic Predisposition to Disease epidemiology, Heterozygote, Liver Cirrhosis, Alcoholic genetics, alpha 1-Antitrypsin genetics
- Abstract
Objective: Homozygous alpha1-antitrypsin (AAT) deficiency increases the risk for developing cirrhosis, whereas the relevance of heterozygous carriage remains unclear. Hence, we evaluated the impact of the two most relevant AAT variants ('Pi*Z' and 'Pi*S'), present in up to 10% of Caucasians, on subjects with non-alcoholic fatty liver disease (NAFLD) or alcohol misuse., Design: We analysed multicentric case-control cohorts consisting of 1184 people with biopsy-proven NAFLD and of 2462 people with chronic alcohol misuse, both cohorts comprising cases with cirrhosis and controls without cirrhosis. Genotyping for the Pi*Z and Pi*S variants was performed., Results: The Pi*Z variant presented in 13.8% of patients with cirrhotic NAFLD but only in 2.4% of counterparts without liver fibrosis (p<0.0001). Accordingly, the Pi*Z variant increased the risk of NAFLD subjects to develop cirrhosis (adjusted OR=7.3 (95% CI 2.2 to 24.8)). Likewise, the Pi*Z variant presented in 6.2% of alcohol misusers with cirrhosis but only in 2.2% of alcohol misusers without significant liver injury (p<0.0001). Correspondingly, alcohol misusers carrying the Pi*Z variant were prone to develop cirrhosis (adjusted OR=5.8 (95% CI 2.9 to 11.7)). In contrast, the Pi*S variant was not associated with NAFLD-related cirrhosis and only borderline with alcohol-related cirrhosis (adjusted OR=1.47 (95% CI 0.99 to 2.19))., Conclusion: The Pi*Z variant is the hitherto strongest single nucleotide polymorphism-based risk factor for cirrhosis in NAFLD and alcohol misuse, whereas the Pi*S variant confers only a weak risk in alcohol misusers. As 2%-4% of Caucasians are Pi*Z carriers, this finding should be considered in genetic counselling of affected individuals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2019
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13. Habitable Climate Scenarios for Proxima Centauri b with a Dynamic Ocean.
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Del Genio AD, Way MJ, Amundsen DS, Aleinov I, Kelley M, Kiang NY, and Clune TL
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- Exobiology, Greenhouse Gases, Water Movements, Atmosphere, Climate, Models, Theoretical, Oceans and Seas, Planets
- Abstract
The nearby exoplanet Proxima Centauri b will be a prime future target for characterization, despite questions about its retention of water. Climate models with static oceans suggest that Proxima b could harbor a small dayside surface ocean despite its weak instellation. We present the first climate simulations of Proxima b with a dynamic ocean. We find that an ocean-covered Proxima b could have a much broader area of surface liquid water but at much colder temperatures than previously suggested, due to ocean heat transport and/or depression of the freezing point by salinity. Elevated greenhouse gas concentrations do not necessarily produce more open ocean because of dynamical regime transitions between a state with an equatorial Rossby-Kelvin wave pattern and a state with a day-night circulation. For an evolutionary path leading to a highly saline ocean, Proxima b could be an inhabited, mostly open ocean planet with halophilic life. A freshwater ocean produces a smaller liquid region than does an Earth salinity ocean. An ocean planet in 3:2 spin-orbit resonance has a permanent tropical waterbelt for moderate eccentricity. A larger versus smaller area of surface liquid water for similar equilibrium temperature may be distinguishable by using the amplitude of the thermal phase curve. Simulations of Proxima Centauri b may be a model for the habitability of weakly irradiated planets orbiting slightly cooler or warmer stars, for example, in the TRAPPIST-1, LHS 1140, GJ 273, and GJ 3293 systems.
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- 2019
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14. CLIMATE MODELING OF A POTENTIAL EXOVENUS.
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Kane SR, Ceja AY, Way MJ, and Quintana EV
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The planetary mass and radius sensitivity of exoplanet discovery capabilities has reached into the terrestrial regime. The focus of such investigations is to search within the Habitable Zone where a modern Earth-like atmosphere may be a viable comparison. However, the detection bias of the transit and radial velocity methods lies close to the host star where the received flux at the planet may push the atmosphere into a runaway greenhouse state. One such exoplanet discovery, Kepler-1649b, receives a similar flux from its star as modern Venus does from the Sun, and so was categorized as a possible exoVenus. Here we discuss the planetary parameters of Kepler-1649b with relation to Venus to establish its potential as a Venus analog. We utilize the general circulation model ROCKE-3D to simulate the evolution of the surface temperature of Kepler-1649b under various assumptions, including relative atmospheric abundances. We show that in all our simulations the atmospheric model rapidly diverges from temperate surface conditions towards a runaway greenhouse with rapidly escalating surface temperatures. We calculate transmission spectra for the evolved atmosphere and discuss these spectra within the context of the James Webb Space Telescope (JWST) Near-Infrared Spectrograph (NIRSpec) capabilities. We thus demonstrate the detectability of the key atmospheric signatures of possible runaway greenhouse transition states and outline the future prospects of characterizing potential Venus analogs.
- Published
- 2018
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15. Climates of Warm Earth-like Planets I: 3-D Model Simulations.
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Way MJ, Del Genio AD, Aleinov I, Clune TL, Kelley M, and Kiang NY
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We present a large ensemble of simulations of an Earth-like world with increasing insolation and rotation rate. Unlike previous work utilizing idealized aquaplanet configurations we focus our simulations on modern Earth-like topography. The orbital period is the same as modern Earth, but with zero obliquity and eccentricity. The atmosphere is 1 bar N
2 -dominated with CO2 =400 ppmv and CH4 =1 ppmv. The simulations include two types of oceans; one without ocean heat transport (OHT) between grid cells as has been commonly used in the exoplanet literature, while the other is a fully coupled dynamic bathtub type ocean. The dynamical regime transitions that occur as day length increases induce climate feedbacks producing cooler temperatures, first via the reduction of water vapor with increasing rotation period despite decreasing shortwave cooling by clouds, and then via decreasing water vapor and increasing shortwave cloud cooling, except at the highest insolations. Simulations without OHT are more sensitive to insolation changes for fast rotations while slower rotations are relatively insensitive to ocean choice. OHT runs with faster rotations tend to be similar with gyres transporting heat poleward making them warmer than those without OHT. For slower rotations OHT is directed equator-ward and no high latitude gyres are apparent. Uncertainties in cloud parameterization preclude a precise determination of habitability but do not affect robust aspects of exoplanet climate sensitivity. This is the first paper in a series that will investigate aspects of habitability in the simulations presented herein. The datasets from this study are opensource and publicly available.- Published
- 2018
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16. Reply to: "The PNPLA3 SNP rs738409:G allele is associated with increased liver disease-associated mortality but reduced overall mortality in a population-based cohort".
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Atkinson SR, Way MJ, McQuillin A, Morgan MY, and Thursz MR
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- Alleles, Cohort Studies, Humans, Liver Diseases
- Published
- 2018
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17. Homozygosity for rs738409:G in PNPLA3 is associated with increased mortality following an episode of severe alcoholic hepatitis.
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Atkinson SR, Way MJ, McQuillin A, Morgan MY, and Thursz MR
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- Female, Genotype, Hepatitis, Alcoholic mortality, Homozygote, Humans, Male, Polymorphism, Single Nucleotide, Proportional Hazards Models, Hepatitis, Alcoholic genetics, Lipase genetics, Membrane Proteins genetics
- Abstract
Background & Aims: Carriage of rs738409:G in PNPLA3 is associated with an increased risk of developing alcohol-related cirrhosis and has a significant negative effect on survival. Short-term mortality in patients with severe alcoholic hepatitis is high; drinking behaviour is a major determinant of outcome in survivors. The aim of this study was to determine whether carriage of rs738409:G has an additional detrimental effect on survival in this patient group., Methods: Genotyping was undertaken in 898 cases with severe alcoholic hepatitis, recruited through the UK Steroids or Pentoxifylline for Alcoholic Hepatitis (STOPAH) trial, and 1188 White British/Irish alcohol dependent controls with no liver injury, recruited via University College London. Subsequent drinking behaviour was classified, in cases surviving ≥90days, as abstinent or drinking. The relationship between rs738409 genotype, drinking behaviour and survival was explored., Results: The frequency of rs738409:G was significantly higher in cases than controls (29.5% vs. 18.9%; p=2.15×10
-15 ; odds ratio 1.80 [95% confidence interval (CI) 1.55-2.08]). Case-mortality at days 28, 90 and 450 was 16%, 25% and 41% respectively. There was no association between rs738409:G and 28-day mortality. Mortality in the 90 to 450-day period was higher in survivors who subsequently resumed drinking (hazard ratio [HR] 2.77, 95% CI 1.79-4.29; p<0.0001) and in individuals homozygous for rs738409:G (HR 1.69, 95% CI 1.02-2.81, p=0.04)., Conclusion: Homozygosity for rs738409:G in PNPLA3 confers significant additional risk of medium-term mortality in patients with severe alcoholic hepatitis. Rs738409 genotype may be taken into account when considering treatment options for these patients., Lay Summary: Individuals misusing alcohol who carry a particular variant of the gene PNPLA3 are more at risk of developing severe alcoholic hepatitis, a condition with a poor chance of survival. The longer-term outcome in people with this condition who survive the initial illness is strongly influenced by their ability to remain abstinent from alcohol. However, carriers of this gene variant are less likely to survive even if they are able to stop drinking completely. Knowing if someone carries this gene variant could influence the way in which they are managed. Clinical trial numbers: EudraCT reference number: 2009-013897-42; ISRCTN reference number: ISRCTN88782125., Clinical Trial Numbers: EudraCT reference number: 2009-013897-42; ISRCTN reference number: ISRCTN88782125., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)- Published
- 2017
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18. Genetic variants in ALDH1B1 and alcohol dependence risk in a British and Irish population: A bioinformatic and genetic study.
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Way MJ, Ali MA, McQuillin A, and Morgan MY
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- Aldehyde Dehydrogenase chemistry, Aldehyde Dehydrogenase 1 Family, Aldehyde Dehydrogenase, Mitochondrial, Alleles, Case-Control Studies, Genetic Markers, Humans, Ireland, Molecular Dynamics Simulation, Mutation, Missense genetics, Polymorphism, Single Nucleotide, Risk Factors, Structural Homology, Protein, United Kingdom, Alcoholism enzymology, Alcoholism genetics, Aldehyde Dehydrogenase genetics, Computational Biology, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation
- Abstract
Alcohol is metabolized in the liver via the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Polymorphisms in the genes encoding these enzymes, which are common in East Asian populations, can alter enzyme kinetics and hence the risk of alcohol dependence and its sequelae. One of the most important genetic variants, in this regards, is the single nucleotide polymorphism (SNP) rs671 in ALDH2, the gene encoding the primary acetaldehyde metabolizing enzyme ALDH2. However, the protective allele of rs671 is absent in most Europeans although ALDH1B1, which shares significant sequence homology with ALDH2, contains several, potentially functional, missense SNPs that do occur in European populations. The aims of this study were: (i) to use bioinformatic techniques to characterize the possible effects of selected variants in ALDH1B1 on protein structure and function; and, (ii) to genotype three missense and one stop-gain, protein-altering, non-synonymous SNPs in 1478 alcohol dependent cases and 1254 controls of matched British and Irish ancestry. No significant allelic associations were observed between the three missense SNPs and alcohol dependence risk. The minor allele frequency of rs142427338 (Gln378Ter) was higher in alcohol dependent cases than in controls (allelic P = 0.19, OR = 2.98, [0.62-14.37]) but as this SNP is very rare the study was likely underpowered to detect an association with alcohol dependence risk. This potential association will needs to be further evaluated in other large, independent European populations.
- Published
- 2017
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19. Genetic variation in GABRβ1 and the risk for developing alcohol dependence.
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McCabe WA, Way MJ, Ruparelia K, Knapp S, Ali MA, Anstee QM, Thomas HC, McQuillin A, and Morgan MY
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- Adult, Aged, Aged, 80 and over, Alleles, Female, GA-Binding Protein Transcription Factor metabolism, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Haplotypes, Humans, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, White People genetics, Alcoholism genetics, GA-Binding Protein Transcription Factor genetics
- Abstract
Associations between the γ-aminobutyric acid type-A receptors (GABAA) and alcohol dependence risk have been reported, although the receptor subunit driving the association is unclear. Recent work in mice has highlighted a possible role for variants in the Gabr β1 subunit (Gabrβ1) in alcohol dependence risk, although this gene does not contain any common nonsynonymous variants in humans. However, the GABAA receptor is a heteropentamer so multiple potential variants within the gene complex could generate the alcohol dependence phenotype. The association between GABRβ1 variants and alcohol dependence risk was explored in a British and Irish population of alcohol-dependent cases (n=450) and ancestrally-matched controls screened to exclude current or historical alcohol misuse (n=555). Twelve common single nucleotide polymorphisms (SNPs) and a rare nonsynonymous variant, rs41311286, were directly genotyped; imputation was then performed across the whole gene. No allelic association was observed between alcohol dependence risk and any of the directly genotyped or imputed SNPs. However, post-hoc testing for genotypic association identified five common intronic SNPs that showed modest evidence for association after correction for multiple testing; two, rs76112682 and rs141719901, were in complete linkage disequilibrium [Pcorrected=0.02, odds ratio (95% confidence interval)=5.9 (1.7-2.06)]. These findings provide limited support for an association between GABRβ1 and the risk for developing alcohol dependence; further testing in expanded cohorts may be warranted.
- Published
- 2017
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20. STRUCTURE IN THE 3D GALAXY DISTRIBUTION: III. FOURIER TRANSFORMING THE UNIVERSE: PHASE AND POWER SPECTRA.
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Scargle JD, Way MJ, and Gazis PR
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We demonstrate the effectiveness of a relatively straightforward analysis of the complex 3D Fourier transform of galaxy coordinates derived from redshift surveys. Numerical demonstrations of this approach are carried out on a volume-limited sample of the Sloan Digital Sky Survey redshift survey. The direct unbinned transform yields a complex 3D data cube quite similar to that from the Fast Fourier Transform (FFT) of finely binned galaxy positions. In both cases deconvolution of the sampling window function yields estimates of the true transform. Simple power spectrum estimates from these transforms are roughly consistent with those using more elaborate methods. The complex Fourier transform characterizes spatial distributional properties beyond the power spectrum in a manner different from (and we argue is more easily interpreted than) the conventional multi-point hierarchy. We identify some threads of modern large scale inference methodology that will presumably yield detections in new wider and deeper surveys.
- Published
- 2017
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21. Was Venus the First Habitable World of our Solar System?
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Way MJ, Del Genio AD, Kiang NY, Sohl LE, Grinspoon DH, Aleinov I, Kelley M, and Clune T
- Abstract
Present-day Venus is an inhospitable place with surface temperatures approaching 750K and an atmosphere 90 times as thick as Earth's. Billions of years ago the picture may have been very different. We have created a suite of 3-D climate simulations using topographic data from the Magellan mission, solar spectral irradiance estimates for 2.9 and 0.715 Gya, present-day Venus orbital parameters, an ocean volume consistent with current theory, and an atmospheric composition estimated for early Venus. Using these parameters we find that such a world could have had moderate temperatures if Venus had a rotation period slower than ~16 Earth days, despite an incident solar flux 46-70% higher than Earth receives. At its current rotation period, Venus's climate could have remained habitable until at least 715 million years ago. These results demonstrate the role rotation and topography play in understanding the climatic history of Venus-like exoplanets discovered in the present epoch.
- Published
- 2016
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22. Phenotypic heterogeneity in study populations may significantly confound the results of genetic association studies on alcohol dependence.
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Ali MA, Way MJ, Marks M, Guerrini I, Thomson AD, Strang J, McQuillin A, and Morgan MY
- Subjects
- Alcoholism ethnology, Alcoholism pathology, Alcoholism psychology, Case-Control Studies, Female, Fibrosis etiology, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Phenotype, Polymorphism, Single Nucleotide, White People genetics, Alcoholism genetics, Carrier Proteins genetics, Fibrosis genetics
- Abstract
Background: The interpretation of genetic studies on alcohol dependence may be confounded by the co-occurrence of substance dependence, psychiatric disorders and alcohol-related comorbidities, for example, cirrhosis. Significant single-marker and haplotypic associations between polymorphisms in the zinc finger gene, ZNF699, and alcohol dependence were reported in the Irish Affected Sib Pair Study of Alcohol Dependence population, one-third of whom had co-occurring substance dependence while 80% had identified psychiatric comorbidity. The aim of this study was to explore variant ZNF699 associations with alcohol dependence while exercising controls for potential confounders., Methods: The study population was comprised of 1449 alcohol-dependent cases and 1283 population controls; all were of British or Irish ancestry. None of the cases had a history of dependence on other substances, and the frequency of comorbid depression was low. A separate, ancestry-matched cohort of 196 opioid-dependent cases was also included. Genotyping for the four previously identified SNPs of interest in ZNF699 was performed using K-Biosciences Competitive Allele Specific PCR., Results: No single-marker associations were found between polymorphisms in ZNF699 and alcohol dependence per se. A significant allelic association was found between rs7254880 in ZNF699 and alcohol-related cirrhosis (n=292), using cases with no biopsy evidence of liver disease (n=314) as controls (P=0.013). Significant allelic associations were also found between rs12460279 (P=0.028), rs7252865 (P=0.012) and rs10854142 (P=0.016) in ZNF699 and opioid dependence., Conclusion: Phenotypic variation in study populations may contribute towards the nonreplication of genetic association studies on alcohol dependence; controls for recognised confounding variables should be exercised whenever possible.
- Published
- 2015
- Full Text
- View/download PDF
23. The functional GRM3 Kozak sequence variant rs148754219 affects the risk of schizophrenia and alcohol dependence as well as bipolar disorder.
- Author
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O'Brien NL, Way MJ, Kandaswamy R, Fiorentino A, Sharp SI, Quadri G, Alex J, Anjorin A, Ball D, Cherian R, Dar K, Gormez A, Guerrini I, Heydtmann M, Hillman A, Lankappa S, Lydall G, O'Kane A, Patel S, Quested D, Smith I, Thomson AD, Bass NJ, Morgan MY, Curtis D, and McQuillin A
- Subjects
- Humans, Alcoholism genetics, Bipolar Disorder genetics, Genetic Predisposition to Disease, Schizophrenia genetics
- Published
- 2014
- Full Text
- View/download PDF
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