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.

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.

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.

A statistical mechanical model of the lipid bilayer above its phase transition.

A statistical mechanical model of a bilayer of dipalmitoyl-3-sn-phosphatidylcholine molecules above their phase transition is presented. A molecular field approximation developed in previous work by Marcelja is extended by setting the molecular field at each depth in the bilayer in proportion to the average chain order at that depth. The free energy of the hydrocarbon/water interface and that due to the interaction of the polar headgroups is included in the evaluation of the statistical weights of the chain conformations. The model gives good agreement with several independent experimental results. It resolves the dilemma posed by the experimental evidence that there is (i) a considerable variation in order parameter along the lipid chain, but (ii) no collective tilt in the more ordered region of the chain. The model gives an explanation of how the lipid chains pack under these two constraints. The order parameter profile down the chain does not correspond to the profile across the bilayer.

Lateral tensions and pressures in membranes and lipid monolayers.

The effects of lateral tension on the properties of membranes are often explained in comparison with analogous experiments on monolayers, which yield more detailed data. To calculate the effects of changes in tension on the composition of, or incorporation of amphiphiles into membranes we examine (i) the fidelity of the monolayer analogy, (ii) the range of possible tensions in a membrane, and the way in which tensions arise and (iii) the equilibrium partitioning of amphiphiles between aqueous solution and a bilayer under tension. We argue that, at the same areas per molecule, a monolayer at an n-alkane/water interface is a closer analogy of the lipid bilayer than a monolayer at an air/water interface. Next, we show from a thermodynamic argument that changes in membrane tension can affect the absorption of very large amphiphiles such as proteins, but that physiological tensions are unlikely to affect the absorption of lipids or drugs. Finally we consider the possibility that the measured bulk tension in a complicated membrane such as that of the erythrocyte may be larger than the local tension in the fluid mosaic portions, and suggest a model which explains the ability of the erythrocyte membrane to withstand much higher tensions than other biological membranes and lipid bilayers.

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.

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.

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.

A prospective study of sex hormone-binding globulin and fatal cardiovascular disease in Rancho Bernardo men and women.

Sex hormone-binding globulin (SHBG) has been shown to be associated with several cardiovascular disease (CVD) risk factors. We examined the prospective association between SHBG and the risk of CVD and ischemic heart disease (IHD) death in 760 men and 624 women, aged 50-82 yr, who were free of heart disease at baseline. Health status and cause of death were determined annually for 99.9% of the cohort for 19 yr. SHBG correlated negatively with body mass index in both sexes and increased with age in men. After adjusting for age and body mass index, SHBG correlated negatively with fasting plasma glucose in men and women and with total cholesterol and triglycerides in men. There were 235 CVD and 134 IHD deaths in men and 153 CVD and 80 IHD deaths in women over the 19-yr follow-up. The quintile of baseline SHBG was unrelated to CVD or IHD mortality rate. No association was found in sex-specific, multiply-adjusted Cox proportional hazard models. All risk ratios were close to 1, and 95% confidence intervals were narrow and included 1. Although associated with several strong heart disease risk factors, the SHBG level does not predict CVD or IHD mortality in men or women.

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.

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.

Prevalence of nonclassical steroid 21-hydroxylase deficiency based on a morning salivary 17-hydroxyprogesterone screening test: a small sample study.

Early morning salivary 17 alpha-hydroxyprogesterone (17-OHP) determination differentiates patients with non-classical 21-hydroxylase deficiency (NC21OHD) from those who are not affected. Using this test, we have conducted a trial screening study for NC21OHD and have compared the study results with previously reported figures for the frequency of this disorder. Testing was performed on 258 subjects recruited from among the medical students and employees of the New York Hospital-Cornell Medical Center. In 2 of the 249 admissible subjects, the 0700-0900 h salivary 17-OHP level was within the range for NC21OHD patients (0.72-6.7 nmol/L; n = 8). These 2 individuals were subsequently confirmed to be affected by ACTH testing. Of the subjects with morning salivary 17-OHP levels below the cut-off point of 0.72 nmol/L, 29 were recalled for ACTH testing and were confirmed to be unaffected. Prevalence of NC21OHD in the test population was determined according to ethnic group. Our study gives a prevalence by screening of 1.14% among caucasians, which agrees with values of 0.81% and 1.06% obtained by different analytical methods. Further, both affected subjects were Ashkenazi Jews, and the prevalence of 3.23% among study members from this group concurs with increased rates of 3.64% and 4.97% already reported. On the basis of a small population sample, screening so far confirms the claim that NC21OHD is the most common autosomal recessive human disorder. Using values from ACTH-proven unaffected subjects (n = 47) and NC21OHD patients (n = 10), we establish preliminary normative data for morning salivary 17-OHP levels of 0.172 nmol/L for unaffected subjects (95% confidence interval, 0.05-0.54 nmol/L) and 1.76 nmol/L for NC21OHD-affected subjects (95% confidence interval, 0.42-7.32 nmol/L).

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.

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.

The epidemiology of DHEAS and cardiovascular disease.

In 1986 we reported that high levels of plasma dehydroepiandrosterone sulfate (DHEAS) reduced the risk of fatal cardiovascular disease (CVD) in 242 men and increased the risk in 289 women from the Rancho Bernardo cohort who were followed up for 12 years. We report here an update on the epidemiology of DHEAS and CVD based on a 19-year follow-up of 1,029 men and 942 women aged 30-88 years from the same cohort. In cross-sectional analyses, DHEAS levels decreased with age in both sexes and were lower in women than men. Men who were overweight were more likely to have low DHEAS levels; women who had hypercholesterolemia or hypertension or were nonusers of estrogen therapy had higher DHEAS levels. Alcohol intake and cigarette smoking were associated with higher DHEAS levels in both sexes. All differences were no longer statistically significant after adjusting for alcohol intake. All participants were followed for vital status. After 19 years there were 254 CVD deaths in men and 199 CVD deaths in women. DHEAS was not associated with CVD or ischemic heart disease (IHD) deaths in age-adjusted analyses where the comparison group was individuals without CVD or IHD death. In contrast, when the comparison group was survivors, multiply adjusted models showed a statistically significant, modestly reduced risk of fatal CVD (RR = 0.85) in men and a nonsignificant increased risk of fatal CVD (RR = 1.11) in women.

Prospective study of endogenous sex hormones and fatal cardiovascular disease in postmenopausal women.

OBJECTIVES: To examine the association between androstenedione, total and bioavailable testosterone, oestrone, and total and bioavailable oestradiol concentrations and the risk of death from cardiovascular and ischaemic heart disease. DESIGN: 19 year old population based prospective study with 99.9% follow up. SETTING: Rancho Bernardo, California. SUBJECTS: 651 postmenopausal women, none taking oestrogen. MAIN OUTCOME MEASURES: Concentrations of plasma sex hormones measured by radioimmunoassay in an endocrinology research laboratory. Cardiovascular and ischaemic heart disease deaths assessed by death certificate; 85% of 30% sample validated by record review. RESULTS: Age adjusted concentrations of sex hormones did not differ significantly in women with and without a history of heart disease at baseline and did not predict cardiovascular death or death from ischaemic heart disease. Most 95% confidence intervals for the age adjusted relative risk of cardiovascular death or death from ischaemic heart disease were narrow, and all included one. Endogenous oestrogen concentrations were not associated with significantly more favourable risk factors for heart disease, and testosterone was not associated with less favourable risk factors. CONCLUSION: These prospective data do not support a causal or preventive role for endogenous oestrogens or androgens and cardiovascular mortality in older women.

A group psychotherapy approach to postpartum depression.

In this article, the current knowledge of postpartum depression is reviewed, leading to an understanding of this form of depression as an expression of psychosocial factors compounded by the biological changes of the puerperium. A rationale for treating women in the context of the postpartum period is described. A novel approach to treatment is presented. The treatment uses the medium of group psychotherapy to administer interventions. The interventions are introduced in three phases across six months in weekly group sessions. The systematic intervention program focuses on decreasing four symptoms common to postpartum depression: depressed feelings, anxiety, distress, and low self-esteem. Spouses are involved in the treatment plan from the onset, participating in assessment sessions and in a couples group.