Coronary Artery Calcification (CAC) and Post-Trial Cardiovascular Events and Mortality Within the Women's Health Initiative (WHI) Estrogen-Alone Trial.

BackgroundAmong women aged 50 to 59 years at baseline in the Women's Health Initiative (WHI) Estrogen-Alone (E-Alone) trial, randomization to conjugated equine estrogen-alone versus placebo was associated with lower risk of myocardial infarction and mortality, and, in an ancillary study, the WHI-CACS (WHI Coronary Artery Calcification Study) with lower CAC, measured by cardiac computed tomography ≈8.7 years after baseline randomization. We hypothesized that higher CAC would be related to post-trial coronary heart disease (CHD), cardiovascular disease (CVD), and total mortality, independent of baseline randomization or risk factors.Methods and resultsWHI-CACS participants (n=1020) were followed ≈8 years from computed tomography scan in 2005 (mean age=64.4) through 2013 for incident CHD (myocardial infarction and fatal CHD, n=17), CVD (n=69), and total mortality (n=55). Incident CHD and CVD analyses excluded women with CVD before scan (n=89). Women with CAC=0 (n=54%) had very low age-adjusted rates/1000 person-years of CHD (0.91), CVD (5.56), and mortality (3.45). In comparison, rates were ≈2-fold higher for women with any CAC (>0). Associations were not modified by baseline randomization to conjugated equine estrogen-alone versus placebo. Adjusted for baseline randomization and risk factors, the hazard ratio (95% confidence interval) for CAC >100 (19%) was 4.06 (2.11, 7.80) for CVD and 2.70 (1.26, 5.79) for mortality.ConclusionsAmong a subset of postmenopausal women aged 50 to 59 years at baseline in the WHI E-Alone Trial, CAC at mean age of 64 years was strongly related to incident CHD, CVD, and to total mortality over ≈8 years, independent of baseline randomization to conjugated equine estrogen-alone versus placebo or CVD risk factors.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00000611

Infrared phonon anomaly and magnetic excitations in single-crystal Cu3Bi(SeO3)2O2Cl

nfrared reflection and transmission as a function of temperature have been measured on single crystals of Cu3Bi(SeO3)2O2Cl. The complex dielectric function and optical properties along all three principal axes of the orthorhombic cell were obtained via Kramers-Kronig analysis and by fits to a Drude-Lorentz model. Below 115 K, 16 additional modes [8(E∥â)+6(E∥b̂)+2(E∥ĉ)] appear in the phonon spectra; however, powder x-ray diffraction measurements do not detect a new structure at 85 K. Potential explanations for the new phonon modes are discussed. Transmission in the far infrared as a function of temperature has revealed magnetic excitations originating below the magnetic ordering temperature (Tc∼24 K). The origin of the excitations in the magnetically ordered state will be discussed in terms of their response to different polarizations of incident light, behavior in externally applied magnetic fields, and the anisotropic magnetic properties of Cu3Bi(SeO3)2O2Cl as determined by dc susceptibility measurements

Global modelling of the early Martian climate under a denser CO2 atmosphere: Water cycle and ice evolution

We discuss 3D global simulations of the early Martian climate that we have performed assuming a faint young Sun and denser CO2 atmosphere. We include a self-consistent representation of the water cycle, with atmosphere-surface interactions, atmospheric transport, and the radiative effects of CO2 and H2O gas and clouds taken into account. We find that for atmospheric pressures greater than a fraction of a bar, the adiabatic cooling effect causes temperatures in the southern highland valley network regions to fall significantly below the global average. Long-term climate evolution simulations indicate that in these circumstances, water ice is transported to the highlands from low-lying regions for a wide range of orbital obliquities, regardless of the extent of the Tharsis bulge. In addition, an extended water ice cap forms on the southern pole, approximately corresponding to the location of the Noachian/Hesperian era Dorsa Argentea Formation. Even for a multiple-bar CO2 atmosphere, conditions are too cold to allow long-term surface liquid water. Limited melting occurs on warm summer days in some locations, but only for surface albedo and thermal inertia conditions that may be unrealistic for water ice. Nonetheless, meteorite impacts and volcanism could potentially cause intense episodic melting under such conditions. Because ice migration to higher altitudes is a robust mechanism for recharging highland water sources after such events, we suggest that this globally sub-zero, `icy highlands' scenario for the late Noachian climate may be sufficient to explain most of the fluvial geology without the need to invoke additional long-term warming mechanisms or an early warm, wet Mars.Comment: Minor revisions to text, one new table, figs. 1,3 11 and 18 redon

Localized precipitation and runoff on Mars

We use the Mars Regional Atmospheric Modeling System (MRAMS) to simulate lake storms on Mars, finding that intense localized precipitation will occur for lake size >=10^3 km^2. Mars has a low-density atmosphere, so deep convection can be triggered by small amounts of latent heat release. In our reference simulation, the buoyant plume lifts vapor above condensation level, forming a 20km-high optically-thick cloud. Ice grains grow to 200 microns radius and fall near (or in) the lake at mean rates up to 1.5 mm/hr water equivalent (maximum rates up to 6 mm/hr water equivalent). Because atmospheric temperatures outside the surface layer are always well below 273K, supersaturation and condensation begin at low altitudes above lakes on Mars. In contrast to Earth lake-effect storms, lake storms on Mars involve continuous precipitation, and their vertical velocities and plume heights exceed those of tropical thunderstorms on Earth. Convection does not reach above the planetary boundary layer for lakes O(10^2) mbar. Instead, vapor is advected downwind with little cloud formation. Precipitation occurs as snow, and the daytime radiative forcing at the land surface due to plume vapor and storm clouds is too small to melt snow directly (<+10 W/m^2). However, if orbital conditions are favorable, then the snow may be seasonally unstable to melting and produce runoff to form channels. We calculate the probability of melting by running thermal models over all possible orbital conditions and weighting their outcomes by probabilities given by Laskar et al., 2004. We determine that for an equatorial vapor source, sunlight 15% fainter than at present, and snowpack with albedo 0.28 (0.35), melting may occur with 4%(0.1%) probability. This rises to 56%(12%) if the ancient greenhouse effect was modestly (6K) greater than today.Comment: Submitted to JGR Planet

Evaluational adjectives

This paper demarcates a theoretically interesting class of "evaluational adjectives." This class includes predicates expressing various kinds of normative and epistemic evaluation, such as predicates of personal taste, aesthetic adjectives, moral adjectives, and epistemic adjectives, among others. Evaluational adjectives are distinguished, empirically, in exhibiting phenomena such as discourse-oriented use, felicitous embedding under the attitude verb `find', and sorites-susceptibility in the comparative form. A unified degree-based semantics is developed: What distinguishes evaluational adjectives, semantically, is that they denote context-dependent measure functions ("evaluational perspectives")—context-dependent mappings to degrees of taste, beauty, probability, etc., depending on the adjective. This perspective-sensitivity characterizing the class of evaluational adjectives cannot be assimilated to vagueness, sensitivity to an experiencer argument, or multidimensionality; and it cannot be demarcated in terms of pretheoretic notions of subjectivity, common in the literature. I propose that certain diagnostics for "subjective" expressions be analyzed instead in terms of a precisely specified kind of discourse-oriented use of context-sensitive language. I close by applying the account to `find x PRED' ascriptions

General closed-form basket option pricing bounds

This article presents lower and upper bounds on the prices of basket options for a general class of continuous-time financial models. The techniques we propose are applicable whenever the joint characteristic function of the vector of log-returns is known. Moreover, the basket value is not required to be positive. We test our new price approximations on different multivariate models, allowing for jumps and stochastic volatility. Numerical examples are discussed and benchmarked against Monte Carlo simulations. All bounds are general and do not require any additional assumption on the characteristic function, so our methods may be employed also to non-affine models. All bounds involve the computation of one-dimensional Fourier transforms; hence, they do not suffer from the curse of dimensionality and can be applied also to high-dimensional problems where most existing methods fail. In particular, we study two kinds of price approximations: an accurate lower bound based on an approximating set and a fast bounded approximation based on the arithmetic-geometric mean inequality. We also show how to improve Monte Carlo accuracy by using one of our bounds as a control variate

Body mass index trajectories in young adulthood predict nonâ alcoholic fatty liver disease in middle age: The CARDIA cohort study

Background & AimsNonâ alcoholic fatty liver disease is an epidemic. Identifying modifiable risk factors for nonâ alcoholic fatty liver disease development is essential to design effective prevention programmes. We tested whether 25â year patterns of body mass index change are associated with midlife nonâ alcoholic fatty liver disease.MethodsIn all, 4423 participants from Coronary Artery Risk Development in Young Adults, a prospective populationâ based biracial cohort (age 18â 30), underwent body mass index measurement at baseline (1985â 1986) and 3 or more times over 25 years. At Year 25, 3115 had liver fat assessed by nonâ contrast computed tomography. Nonâ alcoholic fatty liver disease was defined as liver attenuation â ¤40 Hounsfield Units after exclusions. Latent mixture modelling identified 25â year trajectories in body mass index per cent change (%Î ) from baseline.ResultsWe identified four distinct trajectories of BMI%Î : stable (26.2% of cohort, 25â year BMI %Π = 3.1%), moderate increase (46.0%, BMI%Π = 21.7%), high increase (20.9%, BMI%Π = 41.9%) and extreme increase (6.9%, BMI%Π = 65.9%). Y25 nonâ alcoholic fatty liver disease prevalence was higher in groups with greater BMI %Î : 4.1%, 9.3%, 13.0%, and 17.6%, respectively (Pâ trend <.0001). In multivariable analyses, participants with increasing BMI%Î had increasingly greater odds of nonâ alcoholic fatty liver disease compared to the stable group: OR: 3.35 (95% CI: 2.07â 5.42), 7.80 (4.60â 13.23) and 12.68 (6.68â 24.09) for moderate, high and extreme body mass index increase, respectively. Associations were only moderately attenuated when adjusted for baseline or Y25 body mass index.ConclusionsTrajectories of weight gain during young adulthood are associated with greater nonâ alcoholic fatty liver disease prevalence in midlife independent of metabolic covariates and baseline or concurrent body mass index highlighting the importance of weight maintenance throughout adulthood as a target for primary nonâ alcoholic fatty liver disease prevention.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142937/1/liv13603.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142937/2/liv13603_am.pd

Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity

Glucose ingestion after an overnight fast triggers an insulin-dependent, homeostatic program that is altered in diabetes. The full spectrum of biochemical changes associated with this transition is currently unknown. We have developed a mass spectrometry-based strategy to simultaneously measure 191 metabolites following glucose ingestion. In two groups of healthy individuals (n=22 and 25), 18 plasma metabolites changed reproducibly, including bile acids, urea cycle intermediates, and purine degradation products, none of which were previously linked to glucose homeostasis. The metabolite dynamics also revealed insulin's known actions along four key axes—proteolysis, lipolysis, ketogenesis, and glycolysis—reflecting a switch from catabolism to anabolism. In pre-diabetics (n=25), we observed a blunted response in all four axes that correlated with insulin resistance. Multivariate analysis revealed that declines in glycerol and leucine/isoleucine (markers of lipolysis and proteolysis, respectively) jointly provide the strongest predictor of insulin sensitivity. This observation indicates that some humans are selectively resistant to insulin's suppression of proteolysis, whereas others, to insulin's suppression of lipolysis. Our findings lay the groundwork for using metabolic profiling to define an individual's 'insulin response profile', which could have value in predicting diabetes, its complications, and in guiding therapy

The effect of photochemical ageing and initial precursor concentration on the composition and hygroscopic properties of β-caryophyllene secondary organic aerosol

The effect of photochemical ageing and initial precursor concentration on the composition and hygroscopic properties of secondary organic aerosol (SOA) formed during the chamber photo-oxidation of β-caryophyllene/NO_x mixtures were investigated. Nucleation of β-caryophyllene SOA particles occurred almost immediately after oxidation was initiated and led to the formation of fresh SOA with a relatively simpler composition than has been reported for monoterpenes. The SOA yield values ranged from 9.5–26.7% and 30.4–44.5% using a differential mobility particle sizer (DMPS) and an aerosol mass spectrometer (AMS) mass based measurements, respectively. A total of 20 compounds were identified in the SOA by LC-MS/MS, with the most abundant compounds identified as β-caryophyllonic acid and β-caryophyllinic acid/β-nocaryophyllonic acid. The O:C and H:C elemental ratios of products identified in the condensed phase ranged from 0.20 to 1.00 and 1.00 to 2.00, with average values of 0.39 and 1.58, respectively. The increase in the O:C ratio was associated with a decrease in the saturation concentration of the identified compounds. The compounds identified in the lower initial concentration experiments were more oxidised compared to those that were found to be more abundant in the higher initial concentration experiments with average O:C ratios of 0.51 and 0.27, respectively. Photochemical ageing led to a more complex SOA composition with a larger contribution coming from lower molar mass, higher generation products, where both double bonds had been oxidised. This effect was more evident in the experiments conducted using the lower initial precursor concentration; a finding confirmed by the temporal behaviour of key organic mass fragment measured by an Aerosol Mass Spectrometer. Although the composition changed with both initial precursor concentration and ageing, this had no significant measurable effect on the hygroscopic properties of the SOA formed. The latter finding might have been influenced by the difference in pre-treatment of the semivolatile-containing particles prior to their measurements