Please cite this paper as: Tyrosine kinase 2 and interferon regulatory factor 5 polymorphisms are associated with discoid and subacute cutaneous lupus erythematosus. Experimental Dermatology 2010; ...19: 123–131.
: Lupus erythematosus (LE) is a heterogeneous disease ranging from skin‐restricted manifestations to a progressive multisystem disease. The specific skin lesions include chronic cutaneous, subacute cutaneous and acute cutaneous LE. Both genetic and environmental factors are involved in the development of LE. However, reports on the genetic background of cutaneous lupus erythematosus (CLE) forms, namely discoid (DLE) and subacute cutaneous lupus erythematosus (SCLE), are sparse. We investigated whether the known systemic LE (SLE) susceptibility genes also predispose to CLE. Altogether, 219 Finnish patients with DLE or SCLE and 356 healthy controls were recruited. Single nucleotide polymorphisms tagging reported risk genes were genotyped. Tyrosine kinase 2 (TYK2) rs2304256 was associated with increased risk of DLE (P = 0.012, OR = 1.47, 95% CI = 1.01–1.98). Expression of TYK2 was demonstrated by immunohistochemistry in macrophage‐like cells and neutrophils and interferon regulatory factor 5 (IRF5) in macrophage‐ and fibroblast‐like cells of DLE, SCLE and SLE skin. IRF5 rs10954213 showed association with DLE (P = 0.017, OR = 1.40, 95% CI = 1.06–1.86) and SCLE (P = 0.022, OR = 1.87, 95% CI = 1.09–3.21). A haplotype of cytotoxic T‐lymphocyte‐associated protein 4 (CTLA4) showed association with DLE (P = 0.0065, OR = 2.51, 95% CI = 1.25–5.04). Our results show that the TYK2, IRF5 and CTLA4 genes previously associated with SLE also confer risk for DLE and SCLE, suggesting that different LE subphenotypes may share pathogenetic pathways.
The roles of different dietary proteins in the aetiology of type 2 diabetes (T2D) remain unclear. We investigated the associations of dietary proteins with the risk of incident T2D in Finnish men ...from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study. The study included 2332 men aged 42-60 years at the baseline examinations in 1984-1989. Protein intakes were calculated from 4-d dietary records. Incident T2D was determined by self-administered questionnaires, fasting blood glucose measurements, 2-h oral glucose tolerance tests, and with national registers. The multivariable-adjusted risk of T2D on the basis of protein intakes was compared by the Cox proportional hazard ratios (HR). During the mean follow-up of 19·3 years, 432 incident T2D cases were identified. Total, animal, meat or dairy product protein intakes were not associated with risk of T2D when the potential confounders were accounted for. Plant (multivariable-adjusted extreme-quartile HR 0·65; 95 % CI 0·42, 1·00; P trend 0·04) and egg (HR 0·67; 95 % CI 0·44, 1·00; P trend 0·03) protein intakes were associated with a decreased risk of T2D. Adjustments for BMI, plasma glucose and serum insulin slightly attenuated associations. Replacing 1 % energy from carbohydrates with energy from protein was associated with a 5 % (95 % CI 0, 11) increased risk of T2D, but adjustment for fibre intake attenuated the association. Replacing 1 % of energy from animal protein with energy from plant protein was associated with 18 % (95 % CI 0, 32) decreased risk of T2D. This association remained after adjusting for BMI. In conclusion, favouring plant and egg proteins appeared to be beneficial in preventing T2D.
Abstract
Atmospheric escape is a fundamental process that affects the structure, composition, and evolution of many planets. The signatures of escape are detectable on close-in, gaseous exoplanets ...orbiting bright stars, owing to the high levels of extreme-ultraviolet irradiation from their parent stars. The Colorado Ultraviolet Transit Experiment (CUTE) is a CubeSat mission designed to take advantage of the near-ultraviolet stellar brightness distribution to conduct a survey of the extended atmospheres of nearby close-in planets. The CUTE payload is a magnifying near-ultraviolet (2479–3306 Å) spectrograph fed by a rectangular Cassegrain telescope (206 mm × 84 mm); the spectrogram is recorded on a back-illuminated, UV-enhanced CCD. The science payload is integrated into a 6U Blue Canyon Technology XB1 bus. CUTE was launched into a polar, low-Earth orbit on 2021 September 27 and has been conducting this transit spectroscopy survey following an on-orbit commissioning period. This paper presents the mission motivation, development path, and demonstrates the potential for small satellites to conduct this type of science by presenting initial on-orbit science observations. The primary science mission is being conducted in 2022–2023, with a publicly available data archive coming online in 2023.
Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a ...comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual's subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism.
A set of electron density profiles of Saturn's ionosphere acquired by Cassini radio occultations is archived at the NASA Planetary Data System. However, the reference surface that defines zero ...altitude in these profiles is unknown and appears to vary by 1,500 km at fixed latitude. These profiles are immensely valuable for addressing questions pertaining to the vertical structure, meridional structure, diurnal variations, or solar cycle dependence of Saturn's ionosphere, but their value is severely limited by their questionable altitude scales. Here we have resolved this problem by independently generating the set of 60 electron density profiles. These profiles confirm that, as noted by previous authors, the structure of Saturn's ionosphere is highly variable. Nevertheless, the profiles suggest an underlying morphology of a broad layer at relatively high altitude (often at approximately 2,000–3,000 km altitude) and a series of narrower layers at lower altitude (often at approximately 1,000 km altitude). The vertical structure of Saturn's ionosphere depends on latitude and local time. At low latitudes, densities are greater at dusk than at dawn. Conversely, at mid latitudes, densities are greater at dawn than at dusk. The plasma scale height of the topside ionosphere is relatively small at low latitudes. The high, broad ionospheric layer is apparent at mid and high latitudes at both dawn and dusk, but is not present at low latitudes at either dawn or dusk. Total electron content also shows a strong dependence on latitude, with high latitudes having greater values than low and mid latitudes.
Key Points
Sixty Saturn ionospheric electron density profiles have been generated and verified
There appears to be an underlying morphology of a broad layer at relatively high altitude and a series of narrower layers at lower altitude
The vertical structure of Saturn's ionosphere depends on latitude and local time
On 1 February 2016 Titan occulted the three stars in Orion’s belt, as seen from the Casssini spacecraft. The ultraviolet spectrometer on Cassini observed this event with the stars arranged along the ...instrument’s entrance slit. These three stellar occultations probed different latitudes in Titan’s northern hemisphere but similar longitudes. The occultations were also observed simultaneously in the extreme ultraviolet and far ultraviolet regions of the spectrum. Analysis of these measurements provides information on the atmospheric composition and thermal structure. We determine altitude profiles of N2, CH4, C2H2, C2H4, C2H6, C4H2, C6H6, HCN, and HC3N densities along with aerosol extinction. We infer significant variations in latitude for C2H2, C2H4, C4H2, aerosols, and temperature, providing clues to global circulations patterns. The inferred mole fractions of C2H2, C2H4, C4H2, C6H6, HCN, and HC3N are roughly consistent with photochemical model predictions, but C2H2 and C2H4 are over predicted by tens of percent at pressures greater than 10−5 hPa, C4H2 is under predicted by ∼ x2 at most levels, and C6H6 is under predicted by ∼ x2 at pressures less than 10−5 hPa.
•Cassini observed the simultaneous occultations of the 3 stars in Orion’s belt by Titan.•Analysis provides altitude profiles of N2, CH4, C2H2, C2H4, C2H6, C4H2, C6H6, HCN, HC3N, and aerosols.•Latitude variations in C2H2, C2H4, C4H2, Temperature, and aerosol extinction are measured.•The mole fractions of C2H2, C2H4, C4H2, C6H6, HCN, and HC3N agree with model predictions.•Models over predict C2H2 and C2H4 by tens of percent and underpredict C4H2 and C6H6by ∼ x2.
Stellar flares are a frequent occurrence on young low-mass stars around which many detected exoplanets orbit. Flares are energetic, impulsive events, and their impact on exoplanetary atmospheres ...needs to be taken into account when interpreting transit observations. We have developed a model to describe the upper atmosphere of extrasolar giant planets (EGPs) orbiting flaring stars. The model simulates thermal escape from the upper atmospheres of close-in EGPs. Ionisation by solar radiation and electron impact is included and photo-chemical and diffusive transport processes are simulated. This model is used to study the effect of stellar flares from the solar-like G star HD 209458 and the young K star HD 189733 on their respective planets, HD 209458b and HD 189733b. The Sun is used as a proxy for HD 209458, and ϵ Eridani, as a proxy for HD 189733. A hypothetical HD 209458b-like planet orbiting the very active M star AU Microscopii is also simulated. We find that the neutral upper atmosphere of EGPs is not significantly affected by typical flares on HD 209458 and HD 189733. Therefore, stellar flares alone would not cause large enough changes in planetary mass loss to explain the variations in HD 189733b transit depth seen in previous studies, although we show that it may be possible that an extreme stellar proton event could result in the required mass loss. Our simulations do however reveal an enhancement in electron number density in the ionosphere of these planets, the peak of which is located in the layer where stellar X-rays are absorbed. Electron densities are found to reach 2.2 to 3.5 times pre-flare levels and enhanced electron densities last from about 3 to 10 h after the onset of the flare, depending on the composition of the ionospheric layer. The strength of the flare and the width of its spectral energy distribution affect the range of altitudes in the ionosphere that see enhancements in ionisation. A large broadband continuum component in the XUV portion of the flaring spectrum in very young flare stars, such as AU Mic, results in a broad range of altitudes affected in planets orbiting this star. Indeed, as well as the X-ray absorption layer, the layer in which EUV photons are absorbed is also strongly enhanced.
We construct Saturn equatorial neutral temperature and density profiles of H, H2, He, and CH4, between 10−12 and 1 bar using measurements from Cassini’s Ion Neutral Mass Spectrometer (INMS) taken ...during the spacecraft’s final plunge into Saturn’s atmosphere on 15 September 2017, combined with previous deeper atmospheric measurements from the Cassini Composite InfraRed Spectrometer (CIRS) and from the UltraViolet Imaging Spectrograph (UVIS). These neutral profiles are fed into an energy deposition model employing soft X-ray and Extreme UltraViolet (EUV) solar fluxes at a range of spectral resolutions (Δλ=4×10−3nm to 1 nm) assembled from TIMED/SEE, from SOHO/SUMER, and from the Whole Heliosphere Interval (WHI) quiet Sun campaign. Our energy deposition model calculates ion production rate profiles through photo-ionisation and electron-impact ionisation processes, as well as rates of photo-dissociation of CH4. The ion reaction rate profiles we determine are important to obtain accurate ion density profiles, meanwhile methane photo-dissociation is key to initiate complex organic chemical processes. We assess the importance of spectral resolution in the energy deposition model by using a high-resolution H2 photo-absorption cross section, which has the effect of producing additional ionisation peaks near 800 km altitude. We find that these peaks are still formed when using low-resolution (Δλ=1nm) or mid-resolution (Δλ=0.1nm) solar spectra, as long as high-resolution cross sections are included in the model.
•Neutral temperature and density profiles from the final plunge of Cassini into Saturn’s atmosphere•Photoionisation and electron impact production rate profiles of major ions in Saturn’s ionosphere•Photodissociation rate profiles of methane in Saturn’s upper atmosphere•Importance of using a high-resolution H2 photoabsorption cross section vs solar spectrum
AbstractObjectiveTo examine whether physical inactivity is a risk factor for dementia, with attention to the role of cardiometabolic disease in this association and reverse causation bias that arises ...from changes in physical activity in the preclinical (prodromal) phase of dementia.DesignMeta-analysis of 19 prospective observational cohort studies.Data sourcesThe Individual-Participant-Data Meta-analysis in Working Populations Consortium, the Inter-University Consortium for Political and Social Research, and the UK Data Service, including a total of 19 of a potential 9741 studies.Review methodThe search strategy was designed to retrieve individual-participant data from prospective cohort studies. Exposure was physical inactivity; primary outcomes were incident all-cause dementia and Alzheimer’s disease; and the secondary outcome was incident cardiometabolic disease (that is, diabetes, coronary heart disease, and stroke). Summary estimates were obtained using random effects meta-analysis.ResultsStudy population included 404 840 people (mean age 45.5 years, 57.7% women) who were initially free of dementia, had a measurement of physical inactivity at study entry, and were linked to electronic health records. In 6.0 million person-years at risk, we recorded 2044 incident cases of all-cause dementia. In studies with data on dementia subtype, the number of incident cases of Alzheimer’s disease was 1602 in 5.2 million person-years. When measured <10 years before dementia diagnosis (that is, the preclinical stage of dementia), physical inactivity was associated with increased incidence of all-cause dementia (hazard ratio 1.40, 95% confidence interval 1.23 to 1.71) and Alzheimer’s disease (1.36, 1.12 to 1.65). When reverse causation was minimised by assessing physical activity ≥10 years before dementia onset, no difference in dementia risk between physically active and inactive participants was observed (hazard ratios 1.01 (0.89 to 1.14) and 0.96 (0.85 to 1.08) for the two outcomes). Physical inactivity was consistently associated with increased risk of incident diabetes (hazard ratio 1.42, 1.25 to 1.61), coronary heart disease (1.24, 1.13 to 1.36), and stroke (1.16, 1.05 to 1.27). Among people in whom cardiometabolic disease preceded dementia, physical inactivity was non-significantly associated with dementia (hazard ratio for physical activity assessed >10 before dementia onset 1.30, 0.79 to 2.14).ConclusionsIn analyses that addressed bias due to reverse causation, physical inactivity was not associated with all-cause dementia or Alzheimer’s disease, although an indication of excess dementia risk was observed in a subgroup of physically inactive individuals who developed cardiometabolic disease.
•Object-oriented approach for risk and performance assessment of complex systems.•Customized domain-specific features can be included in standard analysis techniques.•Example combines fault tree, ...dynamic process phase, and production function models.•Open data format to define modelling technique, model structure and parameter values.•Applicable to industrial process reliability, availability and performance analyses.
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This paper introduces an Open Modelling approach for Availability and Reliability of Systems (OpenMARS), which is developed for risk and performance assessment of large and complex systems with dynamic behaviours. The approach allows for combining the most common risk assessment and operation modelling techniques. This ensures a high degree of freedom for the modeller to accurately describe the system without limitations imposed by an individual technique. OpenMARS uses a platform-independent tabular format to define the used modelling technique, to create the model structure, and to assign the parameter values. We developed the format to enable a straightforward manual model definition while maintaining database compatibility. This paper also presents our calculation engine for stochastic simulation-based analysis of OpenMARS models. Our intention is to use this approach as a basis for new software. We demonstrate the feasibility of OpenMARS with an example of a multi-state production process that is subject to failures. The example creates a comprehensive system model by combining interconnected failure logic, operation phase, and production function models. We believe that the advanced features of OpenMARS have wide ranging applications for analysis of reliability, performance, and energy efficiency of complex industrial processes.
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