Dark Energy Survey Year 1 Results: Cosmological Constraints from Cluster Abundances, Weak Lensing, and Galaxy Correlations.

We present the first joint analysis of cluster abundances and auto or cross-correlations of three cosmic tracer fields: galaxy density, weak gravitational lensing shear, and cluster density split by optical richness. From a joint analysis (4×2pt+N) of cluster abundances, three cluster cross-correlations, and the auto correlations of the galaxy density measured from the first year data of the Dark Energy Survey, we obtain Ω_{m}=0.305_{-0.038}^{+0.055} and σ_{8}=0.783_{-0.054}^{+0.064}. This result is consistent with constraints from the DES-Y1 galaxy clustering and weak lensing two-point correlation functions for the flat νΛCDM model. Consequently, we combine cluster abundances and all two-point correlations from across all three cosmic tracer fields (6×2pt+N) and find improved constraints on cosmological parameters as well as on the cluster observable-mass scaling relation. This analysis is an important advance in both optical cluster cosmology and multiprobe analyses of upcoming wide imaging surveys.

Constraints on Dark Matter Properties from Observations of Milky Way Satellite Galaxies.

We perform a comprehensive study of Milky Way (MW) satellite galaxies to constrain the fundamental properties of dark matter (DM). This analysis fully incorporates inhomogeneities in the spatial distribution and detectability of MW satellites and marginalizes over uncertainties in the mapping between galaxies and DM halos, the properties of the MW system, and the disruption of subhalos by the MW disk. Our results are consistent with the cold, collisionless DM paradigm and yield the strongest cosmological constraints to date on particle models of warm, interacting, and fuzzy dark matter. At 95% confidence, we report limits on (i) the mass of thermal relic warm DM, m_{WDM}>6.5 keV (free-streaming length, λ_{fs}≲10h^{-1} kpc), (ii) the velocity-independent DM-proton scattering cross section, σ_{0}<8.8×10^{-29} cm^{2} for a 100 MeV DM particle mass [DM-proton coupling, c_{p}≲(0.3 GeV)^{-2}], and (iii) the mass of fuzzy DM, m_{ϕ}>2.9×10^{-21} eV (de Broglie wavelength, λ_{dB}≲0.5 kpc). These constraints are complementary to other observational and laboratory constraints on DM properties.

Detection of Cross-Correlation between Gravitational Lensing and γ Rays.

In recent years, many γ-ray sources have been identified, yet the unresolved component hosts valuable information on the faintest emission. In order to extract it, a cross-correlation with gravitational tracers of matter in the Universe has been shown to be a promising tool. We report here the first identification of a cross-correlation signal between γ rays and the distribution of mass in the Universe probed by weak gravitational lensing. We use data from the Dark Energy Survey Y1 weak lensing data and the Fermi Large Area Telescope 9-yr γ-ray data, obtaining a signal-to-noise ratio of 5.3. The signal is mostly localized at small angular scales and high γ-ray energies, with a hint of correlation at extended separation. Blazar emission is likely the origin of the small-scale effect. We investigate implications of the large-scale component in terms of astrophysical sources and particle dark matter emission.

Effect of 3-nitrooxypropanol on methane and hydrogen emissions, methane isotopic signature, and ruminal fermentation in dairy cows.

The objective of this crossover experiment was to investigate the effect of a methane inhibitor, 3-nitrooxypropanol (3NOP), on enteric methane emission, methane isotopic composition, and rumen fermentation and microbial profile in lactating dairy cows. The experiment involved 6 ruminally cannulated late-lactation Holstein cows assigned to 2 treatments: control and 3NOP (60 mg/kg of feed dry matter). Compared with the control, 3NOP decreased methane emission by 31% and increased hydrogen emission from undetectable to 1.33 g/d. Methane emissions per kilogram of dry matter intake and milk yield were also decreased 34% by 3NOP. Milk production and composition were not affected by 3NOP, except milk fat concentration was increased compared with the control. Concentrations of total VFA and propionate in ruminal fluid were not affected by treatment, but acetate concentration tended to be lower and acetate-to-propionate ratio was lower for 3NOP compared with the control. The 3NOP decreased the molar proportion of acetate and increase those of propionate, butyrate, valerate, and isovalerate. Deuterium-to-hydrogen ratios of methane and the abundance of (13)CH3D were similar between treatments. Compared with the control, minor (4‰) depletion in the (13)C/(12)C ratio was observed for 3NOP. Genus composition of methanogenic archaea (Methanobrevibacter, Methanosphaera, and Methanomicrobium) was not affected by 3NOP, but the proportion of methanogens in the total cell counts tended to be decreased by 3NOP. Prevotella spp., the predominant bacterial genus in ruminal contents in this experiment, was also not affected by 3NOP. Compared with the control, Ruminococcus and Clostridium spp. were decreased and Butyrivibrio spp. was increased by 3NOP. This experiment demonstrated that a substantial inhibition of enteric methane emission by 3NOP in dairy cows was accompanied with increased hydrogen emission and decreased acetate-to-propionate ratio; however, neither an effect on rumen archaeal community composition nor a significant change in the isotope composition of methane was observed.

Carbon ad-dimer defects in carbon nanotubes.

The adsorption of carbon dimers on carbon nanotubes leads to a rich spectrum of structures and electronic structure modifications. Barriers for the formation of carbon dimer induced defects are calculated and found to be considerably lower than those for the Stone-Wales defect. The electronic states introduced by the ad-dimers depend on defect structure and tube type and size. Multiple carbon ad-dimers provide a route to structural engineering of patterned tubes that may be of interest for nanoelectronics.

The Prevalence of von Willebrand disease in women with abnormal uterine bleeding.

Although a common symptom of von Willebrand disease is menorrhagia or metrorrhagia, the prevalence of this inherited bleeding disorder in women with heavy bleeding is not known. This pilot study compared the prevalence rate of von Willebrand disease in women with dysfunctional uterine bleeding with the prevalence rate in the general population. On average, these women bled for 11.5 days per month and experienced heavy bleeding for >16 years. Over 60% had been treated previously for heavy bleeding. One woman was diagnosed with type 1 von Willebrand disease (5% prevalence rate). Larger studies are needed to confirm this increased rate of von Willebrand disease in women with abnormal uterine bleeding.

Cumulative duration of breast-feeding influences cortisol levels in postmenopausal women.

Cortisol levels dramatically increase during pregnancy, peak at birth, and subsequently decline. However, all previous studies examined women during pregnancy and early postpartum. None examined the long-term association of parity and lactation with cortisol levels. We examined the relation of reproductive history to cortisol levels in postmenopausal women. Subjects were 749 women, aged 50-89, who were not using estrogen in 1984-1987 when morning cortisol was measured. Parity was not significantly associated with cortisol. However, women who breast-fed for >12 months had significantly higher cortisol levels than women who breast-fed for shorter durations or not at all (p = 0.003). This association was stronger among women with three or more births. Duration of breast-feeding is a determinant of cortisol levels in postmenopausal women. Because both increased cortisol and increased duration of breast-feeding may play protective roles in certain autoimmune diseases, such as rheumatoid arthritis, we suggest that the beneficial effect of lactation on the course of these diseases may be mediated by cortisol.

Usual dietary isoflavone intake is associated with cardiovascular disease risk factors in postmenopausal women.

Intervention data suggest a cardioprotective role for supplemental isoflavones; however, few studies have examined the cardiovascular disease (CVD) benefit of usual dietary isoflavone intake. This cross-sectional study examined the association between usual dietary isoflavone intake and CVD risk factors, including lipids and lipoproteins, body mass index (BMI) and fat distribution, blood pressure, glucose and insulin. Subjects were postmenopausal women (n = 208) aged 45-74 y, who attended screening and baseline visits for a randomized, double-blind, placebo-controlled trial examining the effects of isoflavone use. At screening, total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol were measured, and demographic, behavioral and menopausal characteristics were assessed. One month later, dietary intake over the past year was assessed with a standardized questionnaire. Anthropometric measurements and blood pressure were obtained, and a 75-g oral glucose tolerance test was administered. Isoflavone consumption did not vary by age, exercise, smoking, education or years postmenopausal. Women with high genistein intake had a significantly lower BMI (P-trend = 0.05), waist circumference (P-trend = 0.05) and fasting insulin (P-trend = 0.07) than those with no daily genistein consumption. In adjusted analyses, genistein, daidzein and total isoflavone intake were each positively associated with HDL cholesterol (P = 0.05) and inversely associated with postchallenge insulin (P = 0.05). These data suggest a protective role for dietary soy intake against CVD in postmenopausal women.

Ability of fat and fat-free mass percentages to predict functional disability in older men and women.

OBJECTIVES: Previous studies suggest an association between body composition and declining functional ability in older people. This study examined the relation between functional disability and percentage of fat mass (FM) and percentage of fat-free mass (FFM) in older men and women. DESIGN: Cross-sectional and prospective. SETTING: Rancho Bernardo, California. PARTICIPANTS: Subjects consisted of 1,051 ambulatory, community-dwelling Caucasian men and women, age 55 to 92, who attended a clinic visit between 1988 and 1992 and a subsequent clinic visit between 1992 and 1996. MEASUREMENTS: Measured at both visits, percentage of fat mass and percentage of lean body mass were estimated by bioelectric impedance analysis and functional disability was ascertained by self-administered questionnaire. Functional disability was dichotomized into those having any difficulty with a set of tasks versus those having no difficulty with the tasks. Two measures of functional disability were used: "lower body" disability, consisting of two lower motor tasks (walking 2-3 blocks and climbing up 10 stairs) and "overall" disability, consisting of nine tasks representing upper and lower body function and mobility. RESULTS: Compared with men, women were more likely to report both lower body and overall functional disability (P=.001). Cross-sectionally, a significant positive association was shown between fat mass and overall functional disability and a significant negative association was shown between FFM and overall functional disability in both men and women. Prospectively, increased percentage of body fat and decreased percentage of FFM were significantly associated with decreased functional ability in both women and men. All results were adjusted for age, smoking, alcohol use, physical activity, current estrogen use, depression, chronic disease, and education. CONCLUSION: Increased percentage of fat mass and decreased percentage of FFM are associated with greater functional disability in older men and women. Further research is needed to assess the relative importance of decreasing fat percentage or increasing fat-free percentage to preserve or improve functional ability in older people.

Sex differences in the association of endogenous sex hormone levels and glucose tolerance status in older men and women.

OBJECTIVE: Some evidence suggests an inverse association between type 2 diabetes and androgens in men and a positive association between type 2 diabetes and androgens in women. The purpose of this community-based study was to evaluate sex differences in the association between endogenous total and bioavailable estrogen and testosterone levels and glucose tolerance status. RESEARCH DESIGN AND METHODS: We included in this study 775 men and 633 postmenopausal non-estrogen-using women, all > or =55 years of age (mean ages 72 and 75 years, respectively). A 75-g oral glucose tolerance test (OGTT) was administered to fasting subjects from 1984 to 1987, when sera were frozen for measurement of total and bioavailable hormone levels. Total testosterone and estradiol levels were measured by radioimmunoassay, and bioavailable hormone levels were determined using a modified ammonium-sulfate precipitation method. The association between steroid hormones and glucose tolerance status was tested. RESULTS: In sex-specific age- and BMI-adjusted analyses, men with impaired glucose tolerance (IGT) had significantly lower total testosterone levels. Women with IGT or type 2 diabetes had significantly higher bioavailable testosterone and total and bioavailable estradiol levels than those with normal glucose tolerance. Total testosterone and fasting plasma glucose were inversely associated in men (P = 0.0001), whereas bioavailable testosterone and estradiol were positively associated with fasting plasma glucose in women (P = 0.0001 and 0.001, respectively). CONCLUSIONS: Additional studies are needed to further develop the hormone-diabetes connection.

Cognitive function and endogenous sex hormones in older women.

OBJECTIVE: To determine if endogenous hormone levels predict cognitive function in older women. DESIGN: A longitudinal, population-based study. SETTING: Rancho Bernardo, California PARTICIPANTS: A total of 393 community-dwelling women aged 55 to 89 years who were not using replacement estrogen. METHODS: Between 1984 and 1987, sera were collected for measurement of total and bioavailable testosterone, total and bioavailable estradiol, and estrone. Between 1988 and 1991, 12 standard neuropsychological tests were administered, including two items from the Blessed Information-Memory-Concentration Test, three measures of retrieval from the Buschke-Fuld Selective Reminding Test, a category fluency test, immediate and delayed recall from the Visual Reproduction Test, the Mini-Mental State Examination (MMSE) with individual analysis of the Serial 7's and the "World" Backwards components, and the Trail-Making Test part B (Trails B). The association between the five hormones and the 12 cognitive function tests was tested in age- and education-adjusted analyses using linear regression, partial correlation, quintile and categorical analyses. RESULTS: Women with better MMSE scores (>23) had significantly higher adjusted mean total and bioavailable testosterone levels (P = .009; P = .02, respectively). Using linear regression, the mean total testosterone was significantly associated with better performance on the World component of the MMSE (b = .12; P = .08). With regard to estrogen, the only statistically significant (P = .02) association was better performance on one test in women with very low levels of estradiol. CONCLUSIONS: In these older women, higher endogenous estrogen levels were not associated with significantly better performance on any cognitive function test. In contrast, higher levels of testosterone predicted better categorical performance on the MMSE and the World component of the MMSE. These novel findings warrant further research.

Endogenous sex hormones and cognitive function in older men.

The objective of this study was to determine whether endogenous sex hormone levels predict cognitive function in older men. Our study design was an exploratory analysis in a population-based cohort in Rancho Bernardo, California. The study participants were 547 community-dwelling men 59-89 yr of age at baseline who were not using testosterone or estrogen therapy. Between 1984 and 1987, sera were collected for measurement of endogenous total and bioavailable testosterone and estradiol levels. Between 1988 and 1991, 12 standard neuropsychological instruments were administered, including two items from the Blessed Information-Memory-Concentration (BIMC) Test, three measures of retrieval from the Buschke-Fuld Selective Reminding Test, a category fluency test, immediate and delayed recall from the Visual Reproduction Test, the Mini-Mental State Examination with individual analysis of the Serial Sevens and the "World" Backwards components, and the Trail-Making Test Part B. In age- and education-adjusted analyses, men with higher levels of total and bioavailable estradiol had poorer scores on the BIMC Test and Mini-Mental State Examination. Men with higher levels of bioavailable testosterone had better scores on the BIMC Test and the Selective Reminding Test (long-term storage). Five associations were U-shaped: total testosterone and total and bioavailable estradiol with the BIMC Test; bioavailable testosterone with the "World" test; and total estradiol with the Trail-Making Test. All associations were relatively weak but independent of age, education, body mass index, alcohol use, cigarette smoking and depression. In these older men, low estradiol and high testosterone levels predicted better performance on several tests of cognitive function. Linear and nonlinear associations were also found, suggesting that an optimal level of sex hormones may exist for some cognitive functions.

Gender differences in insulin-like growth factor and bone mineral density association in old age: the Rancho Bernardo Study.

Insulin-like growth factor-I (IGF-I) clearly plays a role in bone metabolism and maintenance, as evidenced by in vitro and animal studies. In clinical studies, the age-related decrease in IGF-I parallels the age-related decrease in bone mineral density (BMD), but several age-adjusted cross-sectional studies show no consistent association of IGF-I and BMD. We report here a cross-sectional study of serum IGF-I and BMD levels in 483 men and 455 postmenopausal women not using estrogen; subjects were 55 years of age and older, community-dwelling, ambulatory, and unselected for bone density. IGF-I was measured by a highly specific radioimmunoassay. BMD was measured at the lumbar spine and hip using dual-energy X-ray absorptiometry. Men had higher IGF-I and BMD levels than women. In age-adjusted and age-stratified models, IGF-I was associated with BMD only in women (test for interaction, p < 0.0001). Gender differences persisted in gender-specific multiple regression analyses adjusted for age, body mass index, thiazide diuretic use, current smoking, alcohol intake, physical activity, and weight change; IGF-I was significantly associated with BMD at the spine (p = 0.0001) and hip (p = 0.02) in women, but not in men (p's > 0.6). Circulating estradiol levels were not associated with IGF-I levels in either gender, testosterone was inversely associated with IGF-I and only in men. This striking gender difference has not been described previously. Its etiology is unknown. The answer could lead to improved understanding of gender differences in osteoporosis and in response to treatment with IGF-I or growth hormone.

Epidemiology of insulin-like growth factor-I in elderly men and women. The Rancho Bernardo Study.

Insulin-like growth factor-I (IGF-I) is abundant in the circulation and has been shown to have a wide array of biologic effects. The authors carried out a cross-sectional community-based study of 420 men and 419 nonestrogen-using postmenopausal women aged 50-97 years to ascertain the within-person and laboratory reliability of IGF-I measurements, and the association of IGF-I with common epidemiologic confounders. There was no evidence of seasonal or diurnal variation. IGF-I decreased linearly with age in both sexes, with significantly higher levels in men than women (134.1 microg/liter vs. 126.9 microg/liter; p = 0.03) [corrected]. In age-adjusted analyses, IGF-I was not associated with height, total or central body fat, lean body mass, current smoking, physical activity, or commonly used medications. By contrast, in both men and women who reported any alcohol use, IGF-I levels were significantly higher compared with those in men and women who reported no alcohol use, and alcohol as a continuous variable showed a significant positive linear trend in men (p = 0.0007). The authors conclude that IGF-I varied significantly only with age, sex, and alcohol use. The minimal number of confounding variables, good reliability, and little intraindividual variation suggest that IGF-I should be suitable for epidemiologic research.

Sex hormone-binding globulin and glucose tolerance in postmenopausal women. The Rancho Bernardo Study.

OBJECTIVE: Sex hormone-binding globulin (SHBG) has been shown to be associated with several diabetes risk factors, including total body fat, central obesity, and hyperinsulinemic insulin resistance. We examined the cross-sectional association between SHBG and impaired glucose tolerance (IGT) and NIDDM. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study including 657 postmenopausal women, aged > or = 50 years, who were not using hormone replacement therapy. Blood for SHBG and fasting plasma glucose was obtained concurrently in the morning; all women had a 75-g oral glucose tolerance test and measurement of BMI and waist-to-hip ratio (WHR). RESULTS: SHBG was significantly associated with age, BMI, and WHR but not with smoking, physical activity, or alcohol intake. In these women, SHBG was significantly and independently inversely associated with IGT and with NIDDM. CONCLUSIONS: These data strongly support an association between SHBG, or androgenicity, and diabetes in postmenopausal women. Because of the cross-sectional nature of this study, however, the directionality of the association is uncertain.

The effect of postmenopausal estrogen therapy on the risk of non-insulin-dependent diabetes mellitus.

OBJECTIVES: This study examined the effect of postmenopausal estrogen replacement therapy on the incidence of non-insulin-dependent diabetes in women. METHODS: Postmenopausal women aged 50 through 70 years (n=848) without diagnosed diabetes at baseline were followed for 10 to 15 years for incident diabestes. RESULTS: Over the average 11.5 year follow-ip, there were 105 new cases of diabetes. The age-adjusted relative-risk for development of diabetes was nonsignificantly lower for women with continuous estrogen replacement therapy use than for never users. After adjustment for major covariates, a nonsignificant linear trend with increasing duration of estrogen replacement therapy was reversed. CONCLUSIONS: This study suggests that previous results showing a reduced risk of diabetes in women using estrogen may have been due to selection bias regarding who is prescribed estrogen, confounding factors, or differential diagnostic efforts.

Magnetic resonance imaging of myocardial infarction during prothrombin complex concentrate therapy of hemophilia A.

In patients with hemophilia, prothrombin complex concentrates (PCCs) have been successfully used to bypass inhibitors to factor VIII during bleeding episodes. The use of PCCS, including FEIBA (factor eight inhibitor bypassing activity), has been associated with thromboembolic complications. Myocardial infarction (MI) is a rare but serious complication, reported in 13 previous cases, six in the pediatric age group. In all four patients who died during the acute MI, autopsy revealed extensive myocardial hemorrhage. The hearts of three other patients examined at least 5 months after the acute MI showed no evidence of prior hemorrhage. Magnetic resonance (MR) imaging has been shown to be able to evaluate the sequelae of myocardial infarction in adults with coronary artery disease and in children with Kawasaki syndrome. We report the first case of the use of MR imaging in the evaluation of myocardial damage during the acute stage of a FEIBA-associated MI in a 10-year-old boy.

Effect of replacement estrogen on insulin-like growth factor-I in postmenopausal women: the Rancho Bernardo Study.

Insulin-like growth factor-I (IGF-I) is associated with protein, carbohydrate, and bone metabolism. Results of previous studies examining the effect of exogenous estrogen on levels of IGF-I have been inconsistent. We examined the cross-sectional association between serum IGF-I levels and hormone replacement therapy (HRT) use in 672 postmenopausal women aged 50 yr and older. The mean age-adjusted IGF-I level was highest in the 415 women who reported never or past HRT use (126.8 micrograms/L), lowest in the 128 women who reported using estrogen alone (99.3 micrograms/L), and intermediate in the 115 women who reported using combination estrogen and progesterone (112.4 micrograms/L). A significant linear decline in mean age-adjusted IGF-I levels by duration of HRT use among all current users was seen. The decrease in serum IGF-I with current use of HRT is not consistent with the fact that both HRT and increased levels of IGF-I have been associated with improved glucose and bone metabolism and lipid profile. Further research is needed to evaluate the effect of the addition of a progestin to oral HRT on IGF-I-induced changes in GH levels.