Constraining Primordial Black Hole Formation from Single-Field Inflation.

The most widely studied formation mechanism of a primordial black hole is collapse of large-amplitude perturbation on small scales generated in single-field inflation. In this Letter, we calculate one-loop correction to the large-scale power spectrum in a model with sharp transition of the second slow-roll parameter. We find that models producing an appreciable amount of primordial black holes induce nonperturbative coupling on a large scale probed by cosmic microwave background radiation. Our result implies that a small-scale power spectrum can be constrained by large-scale cosmological observations.

Associations between physical physique/fitness in children and bone development during puberty: a 4-year longitudinal study.

Bone growth is most remarkable during puberty. This study aimed to clarify the effects of physique and physical strength on bone mineral density and bone metabolism markers during puberty to help improve bone growth during puberty and prevent future osteoporosis. There were 277 pubertal participants (125 boys and 152 girls) in this survey from 2009 to 2015, all aged 10/11 and 14/15 years. The measures included physical fitness/physique indices (such as muscle ratio etc.), grip strength, bone density (osteo sono-assessment index, OSI), and bone metabolism markers (bone-type alkaline phosphatase and type I collagen cross-linked N-telopeptide). At 10/11-years-old for girls, a positive correlation was found between body size/grip strength and OSI. At 14/15-year-old for boys, all body size factors/grip strength were positively correlated with OSI. The change in body muscle ratio was positively correlated with change in OSI for both sexes. The height, body muscle ratio and grip strength at 10/11-year-old were significantly associated with OSI (positively) and bone metabolism markers (negatively) at 14/15-year-old for both sexes. Adequate physique building after 10/11 years for boys and before 10/11 years for girls may be effective in increasing peak bone mass.

Why Must Primordial Non-Gaussianity Be Very Small?

One-loop correction to the power spectrum in generic single-field inflation is calculated by using standard perturbation theory. Because of the enhancement inversely proportional to the observed red tilt of the spectral index of curvature perturbation, the correction turns out to be much larger than previously anticipated. As a result, the primordial non-Gaussianity must be much smaller than the current observational bound in order to warrant the validity of cosmological perturbation theory.

Constraints on primordial black holes.

We update the constraints on the fraction of the Universe that may have gone into primordial black holes (PBHs) over the mass range 10-5to 1050 g. Those smaller than ∼1015 g would have evaporated by now due to Hawking radiation, so their abundance at formation is constrained by the effects of evaporated particles on big bang nucleosynthesis, the cosmic microwave background (CMB), the Galactic and extragalacticγ-ray and cosmic ray backgrounds and the possible generation of stable Planck mass relics. PBHs larger than ∼1015 g are subject to a variety of constraints associated with gravitational lensing, dynamical effects, influence on large-scale structure, accretion and gravitational waves. We discuss the constraints on both the initial collapse fraction and the current fraction of the dark matter (DM) in PBHs at each mass scale but stress that many of the constraints are associated with observational or theoretical uncertainties. We also consider indirect constraints associated with the amplitude of the primordial density fluctuations, such as second-order tensor perturbations andµ-distortions arising from the effect of acoustic reheating on the CMB, if PBHs are created from the high-σpeaks of nearly Gaussian fluctuations. Finally we discuss how the constraints are modified if the PBHs have an extended mass function, this being relevant if PBHs provide some combination of the DM, the LIGO/Virgo coalescences and the seeds for cosmic structure. Even if PBHs make a small contribution to the DM, they could play an important cosmological role and provide a unique probe of the early Universe.

Relationships between body composition and pulmonary function in a community-dwelling population in Japan.

Pulmonary diseases, including chronic obstructive pulmonary disease (COPD), are major chronic diseases that result in decreased pulmonary function. Relationships between body composition and pulmonary function have been reported. However, few epidemiological studies have used the visceral fat area (VFA) to measure body composition. This study aimed to examine the relationship between body composition and pulmonary function. A cross-sectional study was conducted between 2015 and 2016, using data obtained from 1,287 residents aged between 19 and 91 years living in the Iwaki area of Hirosaki City, a rural region in Aomori Prefecture, Japan. Pulmonary function was evaluated using the forced vital capacity (FVC) as a percentage of the predicted value (predicted FVC%) and the ratio of forced expiratory volume in one second (FEV1) to FVC. The measurements for evaluating body composition included the body fat percentage (BFP) of the whole body and trunk, skeletal muscle index (SMI), body mass index (BMI), VFA, waist circumference (WC) at the navel level, and waist-to-hip ratio (WHR). To adjust for potential confounders, Spearman's partial correlation analysis was used to examine the relationship between the measurements of body composition and pulmonary function. There were significant correlations between the predicted FVC% and the following parameters: BFP (whole body and trunk) in younger males; SMI in older males; WC, VFA, BMI, and SMI in younger females; and BFP (whole body and trunk) and VFA in older females. Contrastingly, WC and VFA in younger males and WC in younger females were correlated with the FEV1/FVC ratio. VFA was correlated with the FEV1/FVC ratio in younger males and predicted FVC% in older females. These findings suggest that visceral fat accumulation may increase the development of obstructive pulmonary disease in young males and accelerate the decline of pulmonary function (predicted FVC%) in older females.

Association between Polyunsaturated Fatty Acid and Reactive Oxygen Species Production of Neutrophils in the General Population.

Little is known about the relationship between polyunsaturated fatty acids (PUFAs) and reactive oxygen species (ROS) in the general population. Therefore this study aimed to describe the association of PUFAs with ROS according to age and sex in the general population and to determine whether PUFA levels are indicators of ROS. This cross-sectional study included 895 participants recruited from a 2015 community health project. Participants were divided into 6 groups based on sex and age (less than 45 years old (young), aged 45-64 years (middle-aged), and 65 years or older (old)) as follows: male, young (n = 136); middle-aged (n = 133); old (n = 82); female, young (n = 159); middle-aged (n = 228); and old (n = 157). The PUFAs measured were arachidonic acid (AA), dihomo gamma linolenic acid (DGLA), AA/DGLA ratio, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ROS considered in the analysis were basal ROS and stimulated ROS levels. Multiple linear analyses showed: (1) significant correlations between PUFA levels, especially DGLA and AA/DGLA ratio, and neutrophil function in the young and middle-aged groups; (2) no significant correlations in old age groups for either sex. Because PUFAs have associated with the ROS production, recommendation for controlled PUFA intake from a young age should be considered.

Toward the detection of gravitational waves under non-Gaussian noises II. Independent component analysis.

We introduce a new analysis method to deal with stationary non-Gaussian noises in gravitational wave detectors in terms of the independent component analysis. First, we consider the simplest case where the detector outputs are linear combinations of the inputs, consisting of signals and various noises, and show that this method may be helpful to increase the signal-to-noise ratio. Next, we take into account the time delay between the inputs and the outputs. Finally, we extend our method to nonlinearly correlated noises and show that our method can identify the coupling coefficients and remove non-Gaussian noises. Although we focus on gravitational wave data analysis, our methods are applicable to the detection of any signals under non-Gaussian noises.

Toward the detection of gravitational waves under non-Gaussian noises I. Locally optimal statistic.

After reviewing the standard hypothesis test and the matched filter technique to identify gravitational waves under Gaussian noises, we introduce two methods to deal with non-Gaussian stationary noises. We formulate the likelihood ratio function under weakly non-Gaussian noises through the Edgeworth expansion and strongly non-Gaussian noises in terms of a new method we call Gaussian mapping where the observed marginal distribution and the two-body correlation function are fully taken into account. We then apply these two approaches to Student's t-distribution which has a larger tails than Gaussian. It is shown that while both methods work well in the case the non-Gaussianity is small, only the latter method works well for highly non-Gaussian case.

Reheating the universe once more: the dissipation of acoustic waves as a novel probe of primordial inhomogeneities on even smaller scales.

We provide a simple but robust bound on the primordial curvature perturbation in the range 10(4) Mpc(-1)

Additive effects of cilnidipine, an L-/N-type calcium channel blocker, and an angiotensin II receptor blocker on reducing cardiorenal damage in Otsuka Long-Evans Tokushima Fatty rats with type 2 diabetes mellitus.

Cilnidipine (Cil), which is an L-/N-type calcium channel blocker (CCB), has been known to provide renal protection by decreasing the activity of the sympathetic nervous system (SNS) and the renin-angiotensin system. In this study, we compared the effects of the combination of Cil and amlodipine (Aml), which is an L-type CCB, with an angiotensin (Ang) II receptor blocker on diabetic cardiorenal damage in spontaneously type 2 diabetic rats. Seventeen-week-old Otsuka Long-Evans Tokushima Fatty rats were randomly assigned to receive Cil, Aml, valsartan (Val), Cil + Val, Aml + Val, or a vehicle (eight rats per group) for 22 weeks. Antihypertensive potencies were nearly equal among the CCB monotherapy groups and the combination therapy groups. The lowering of blood pressure by either treatment did not significantly affect the glycemic variables. However, exacerbations of renal and heart failure were significantly suppressed in rats administered Cil or Val, and additional suppression was observed in those administered Cil + Val. Although Val increased the renin-Ang system, Aml + Val treatment resulted in additional increases in these parameters, while Cil + Val did not show such effects. Furthermore, Cil increased the ratio of Ang-(1-7) to Ang-I, despite the fact that Val and Aml + Val decreased the Ang-(1-7) levels. These actions of Cil + Val might be due to their synergistic inhibitory effect on the activity of the SNS, and on aldosterone secretion through N-type calcium channel antagonism and Ang II receptor type 1 antagonism. Thus, Cil may inhibit the progression of cardiorenal disease in type 2 diabetes patients by acting as an N-type CCB and inhibiting the aldosterone secretion and SNS activation when these drugs were administered in combination with an Ang II receptor blocker.

Effects of low-carbohydrate/high-monounsaturated fatty acid liquid diets on diurnal glucose variability and insulin dose in type 2 diabetes patients on tube feeding who require insulin therapy.

OBJECTIVE: A low-carbohydrate/high-monounsaturated fatty acid liquid diet (LC/HMD) was investigated for its role in long-term glycemic control in tube-fed type 2 diabetes patients who require insulin therapy. PATIENTS AND METHODS: The study included 10 type 2 diabetes patients requiring insulin therapy who were being tube-fed with a high-carbohydrate liquid diet (HCD). With stable glucose control maintained, these patients were monitored for glucose levels for 4 consecutive days by using continuous glucose monitoring (CGM). The patients were continued on HCD during the first 2 days and were switched to an LC/HMD during the final 2 days. The patients were then continued on the LC/HMD, and seven of the 10 patients were monitored for glucose levels for 2 consecutive days by using CGM after 3 months of feeding with the LC/HMD. Insulin regimens used included basal-bolus insulin in five of these seven patients and intermediate-acting insulin in two patients. RESULTS: Based on CGM data, the indices for glucose variability, such as SDs of 288 glucose levels for 24 h, total area for the range of glucose variability, mean amplitude of glycemic excursions, and 24-h mean glucose levels were significantly decreased 3 months after switching from the HCD to the LC/HMD. Additionally, despite the significant decrease in required insulin dose, the hemoglobin A1c (HbA1c) values were significantly decreased 3 months after switching. CONCLUSIONS: Study results demonstrated that the LC/HMD not only narrowed the range of glucose variability, but also decreased the required insulin dose and HbA1c values in diabetes patients on tube feeding who required insulin therapy, suggesting the LC/HMD may be useful in long-term glycemic control in these patients.

Effects of add-on treatment with sitagliptin on narrowing the range of glucose fluctuations in Japanese type 2 diabetes patients receiving insulin therapy.

BACKGROUND: In an earlier continuous glucose monitoring (CGM)-based study, we reported that sitagliptin not only reduced 24-h mean glucose levels but also suppressed postprandial glucose increases, thus reducing the range of glycemic fluctuations in type 2 diabetes patients. In this study, we investigated whether sitagliptin might provide similar benefits in type 2 diabetes patients receiving insulin therapy by using CGM. PATIENTS AND METHODS: The study included a total of 13 type 2 diabetes patients in whom stable glycemic control had been achieved after admission for glycemic control. Insulin regimens used included long-acting insulin preparations once daily in four patients and biphasic insulin preparations twice daily in nine, with the daily insulin dose being 19.0±12.7 U. During the CGM-based study, the patients were given insulin therapy alone on Days 1 and 2 and were given sitagliptin 50 mg/day as add-on treatment on Days 3-6, with their daily insulin doses maintained. RESULTS: The add-on treatment with sitagliptin led to significant decreases in 24-h mean glucose levels and SDs of 288 glucose levels measured by CGM for 24 h, as well as in the indices for magnitude of glucose variability and proportion of time in hyperglycemia, compared with insulin therapy alone (P<0.01), whereas there was no significant change seen in regard to the proportion of time in hypoglycemia with or without add-on treatment with sitagliptin. CONCLUSIONS: This CGM-based study clearly demonstrated that insulin therapy alone, whether with long-acting or biphasic insulin preparations, does not provide adequate glycemic control in type 2 diabetes patients. In contrast, add-on sitagliptin was shown to narrow the range of 24-h glucose fluctuations in these patients, suggesting that add-on treatment with sitagliptin is effective for postprandial glucose control in type 2 diabetes patients receiving insulin therapy.

Cosmology based on f(R) gravity admits 1 eV sterile neutrinos.

It is shown that the tension between recent neutrino oscillation experiments, favoring sterile neutrinos with masses of the order of 1 eV, and cosmological data which impose stringent constraints on neutrino masses from the free streaming suppression of density fluctuations, can be resolved in models of the present accelerated expansion of the Universe based on f(R) gravity.

The effect of a low-carbohydrate/high-monounsaturated fatty acid liquid diet and an isoleucine-containing liquid diet on 24-h glycemic variability in diabetes patients on tube feeding: a comparison by continuous glucose monitoring.

OBJECTIVE: This study compare the effect of various liquid diets on 24-h glycemic variability in diabetes patients on tube feeding. PATIENTS AND METHODS: The study included type 2 diabetes patients in whom percutaneous endoscopic gastrostomy had been performed for dysphagia as a sequela of cerebrovascular disease and who had been put on tube feeding with a standard high-carbohydrate liquid diet (HCD). Once stable glycemic control was achieved, these patients were continuously monitored for glucose levels for 5 days on continuous glucose monitoring. Of the 14 patients included, seven were given HCD on day 1, a low-carbohydrate/high-monounsaturated fatty acid liquid diet (LCD) on Days 2 and 3, and a isoleucine-containing liquid diet (ICD), which is known to promote glycemic uptake by skeletal muscle, thus suppressing increases in glucose levels, on Days 4 and 5, with the remaining seven given the same diets but ICD given on Days 2 and 3 and LCD given on Days 4 and 5. All comparisons were made under the same caloric conditions (caloric intake, 800-1200 kcal/day). RESULTS: The 24-h mean glucose level was significantly lower with LCD and ICD than with HCD but was also significantly lower with LCD than with ICD. On the other hand, the SD of 288 glucose levels over a 24-h period, 24-h total area for glycemic fluctuations, and mean amplitude of glycemic excursion were significantly lower with LCD than with HCD or ICD, whereas they did not differ significantly between HCD and ICD. CONCLUSIONS: LCD and ICD led to significant decreases in mean glucose levels, compared with HCD. However, of the diets compared, LCD had the greatest effect on glycemic variability in these patients on tube feeding.

Effect of miglitol as an add-on to bolus insulin on postprandial glycemic excursions in type 2 diabetes patients assessed by continuous glucose monitoring.

BACKGROUND: We compared the effects of miglitol as an add-on to bolus insulin and dose-intensified bolus insulin on postprandial glycemic excursions by continuous glucose monitoring (CGM). SUBJECTS AND METHODS: The glucose levels of 21 type 2 diabetes patients admitted for glycemic control were monitored for three consecutive days by CGM after stable glycemic control was achieved with bolus or basal-bolus insulin therapy. During the 3-day period, bolus insulin administration was continued in 11 patients on Day 1; the dose of bolus insulin in these patients was increased by 2 U before each meal on day 2, and on day 3, 50 mg of miglitol was administered before each meal in addition to the initial dose of bolus insulin given on Day 1. In the remaining 10 patients, the order of administration on Day 2 and Day 3 was reversed. RESULTS: Of the glycemic fluctuations observed during the 24-h period, postprandial glycemic excursions showed a greater reduction during treatment with dose-intensified bolus insulin and during treatment with miglitol plus bolus insulin than during treatment with bolus insulin alone; however, miglitol plus bolus insulin treatment had a more potent effect than treatment with dose-intensified bolus insulin on reducing postprandial glycemic excursions immediately after meals. Changes in area under the curve (ΔAUC) occurring within 1 h and 2 h after each meal were significantly smaller during treatment with miglitol plus bolus insulin than during treatment with dose-intensified bolus insulin, whereas ΔAUC within >2 h after each meal, except dinner, was significantly greater during treatment with miglitol plus bolus insulin than during treatment with dose-intensified bolus insulin. CONCLUSION: Our findings suggest that miglitol as an add-on to bolus insulin in patients with type 2 diabetes may be one of the beneficial therapeutic options that provides a more rigorous postprandial glycemic control without increasing the risk for hypoglycemia before the next meal.

Primordial non-Gaussianities of gravitational waves in the most general single-field inflation model with second-order field equations.

We completely clarify the feature of primordial non-Gaussianities of tensor perturbations in the most general single-field inflation model with second-order field equations. It is shown that the most general cubic action for the tensor perturbation h(ij) is composed only of two contributions, one with two spacial derivatives and the other with one time derivative on each h(ij). The former is essentially identical to the cubic term that appears in Einstein gravity and predicts a squeezed shape, while the latter newly appears in the presence of the kinetic coupling to the Einstein tensor and predicts an equilateral shape. Thus, only two shapes appear in the graviton bispectrum of the most general single-field inflation model, which could open a new clue to the identification of inflationary gravitational waves in observations of cosmic microwave background anisotropies as well as direct detection experiments.

Liraglutide narrows the range of circadian glycemic variations in Japanese type 2 diabetes patients and nearly flattens these variations in drug-naive type 2 diabetes patients: a continuous glucose monitoring-based study.

BACKGROUND: Liraglutide was examined for its effects on 24-h glucose fluctuations in Japanese type 2 diabetes patients as well as for its differential effects depending on glucose tolerance status after favorable glycemic control was obtained in these patients. PATIENTS AND METHODS: In this prospective open-label pilot study, a total of 20 type 2 diabetes patients hospitalized for glycemic control were given liraglutide 0.3 mg, followed by liraglutide 0.6 mg and 0.9 mg, with each given at 1-week intervals. The patients were continuously monitored for their 24-h glucose levels before treatment and during the course of treatment with liraglutide 0.3 mg, 0.6 mg, and 0.9 mg, respectively, using continuous glucose monitoring (CGM). At the start of treatment with liraglutide, 12 patients were on diet therapy alone, of which six were drug-naive, and eight were being treated with glimepiride. RESULTS: Liraglutide not only significantly reduced 24-h mean glucose levels but also significantly improved all the indices for glycemic variation evaluated, which included SDs of 24-h glucose levels, mean amplitude of glycemic excursions (MAGE), and total area under the glucose fluctuation curve (AUC) for 24 h. The study showed a significant negative correlation for mean glucose levels, SD, and AUC immediately before treatment versus their changes with liraglutide. A 75-g oral glucose tolerance test (OGTT) was given in 11 patients treated with liraglutide monotherapy once favorable glycemic control was achieved. The OGTT revealed that of these, six were found to have normal glucose tolerance, four had impaired glucose tolerance, and one had diabetes, and that of the six drug-naive patients, five patients were found to have normal glucose tolerance, and one had impaired glucose tolerance. CONCLUSIONS: Study results showed that liraglutide is expected not only to reduce mean glucose levels but also to improve 24-h glucose fluctuations, including postprandial glucose excursions, with its effects being particularly conspicuous in patients with early-stage type 2 diabetes.

Influence of telmisartan on insulin response after glucose loading in obese patients with hypertension: ARB trial of hypertension in obese patients with hyperinsulinemia assessed by oral glucose tolerance test (ATHLETE).

INTRODUCTION: The number of patients with both hypertension and obesity has been increasing in Japan. Many of these patients may also have insulin resistance. Telmisartan, an angiotensin II receptor blocker (ARB), selectively activates peroxisome proliferatoractivated receptor (PPAR)-gamma, and this effect is considered to markedly improve insulin resistance in obese patients with hypertension. We compared the antihypertensive and insulin resistance-improving effects of telmisartan with those of candesartan and valsartan in this patient population. METHODS: Twenty-eight elderly patients with an average body mass index (BMI) of 27.1 kg/m(2) were enrolled in this 6-month study. Patients were randomly selected to either switch from candesartan or valsartan to telmisartan or to continue with their current ARB. A 75 g oral glucose tolerance test (OGTT) was performed before and after switching, and the effect of telmisartan on the insulin response to glucose loading was investigated. RESULTS: There was no significant difference in blood pressure between the two groups after drug administration, but glucose tolerance significantly improved in the telmisartan group. The hyperinsulin response to glucose loading also significantly improved in those taking telmisartan, as well as homeostasis model assessment of insulin resistance (HOMA-IR). These changes were not observed in the control group. CONCLUSION: In patients with hypertension and obesity showing insulin resistance, treatment with telmisartan significantly improved the hyperinsulin response to glucose loading. Telmisartan may therefore be beneficial in these patients.

Effects of sitagliptin on 24-h glycemic changes in Japanese patients with type 2 diabetes assessed using continuous glucose monitoring.

BACKGROUND: This study was performed to examine the efficacy of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in Japanese patients with type 2 diabetes using continuous glucose monitoring (CGM) of 24-h glycemic changes. SUBJECTS AND METHODS: The study was a prospective open-label pilot study in patients with type 2 diabetes who were admitted to our hospital and treated with sitagliptin alone or concomitantly with another oral hypoglycemic drug. CGM was performed for 2 days before sitagliptin administration and for another 2 days after administration. The average 24-h blood glucose level, SD of the 24-h blood glucose level, 24-h glycemic fluctuation range, mean amplitude of glycemic excursions (MAGE), and hyperglycemic and hypoglycemic time periods were compared before and after administration. RESULTS: Sitagliptin administration alone and with a concomitant drug decreased the average 24-h blood glucose level, SD of the 24-h blood glucose level, 24-h glycemic fluctuation range, MAGE, and hyperglycemic time, compared with these parameters before administration. There were significant correlations between the average 24-h blood glucose level before administration and the decrease in the average 24-h blood glucose level after administration and between MAGE before administration and the decrease in MAGE after administration. CONCLUSIONS: Sitagliptin decreased the average glycemic level and also improved 24-h glycemic fluctuation, including postprandial hyperglycemia.

Evaluation of efficacy of acarbose on glucose fluctuation and postprandial glucose using continuous glucose monitoring in type 2 diabetes mellitus.

BACKGROUND: The objective of this study was to evaluate the effects of the α-glucosidase inhibitor acarbose on glucose fluctuations in patients with type 2 diabetes using continuous glucose monitoring (CGM). METHODS: CGM was performed for 4 days (72 h), and acarbose at 300 mg/day was administered on two of these days but not on the other two days. The effects on blood glucose fluctuations were evaluated. RESULTS: We recruited a total of 10 patients (five men and five women) with a mean ± SD age of 63.1 ± 12.1 years, body mass index of 22.6 ± 5.4 kg/m(2), and glycohemoglobin of 9.9 ± 1.9%. During treatment with acarbose, significant decreases in median (range) SD of 24-h mean blood glucose (22.48 [6.39-47.22] mg/dL vs. 32.78 [18.83-58.93] mg/dL, P = 0.004), 24-h blood glucose fluctuations (453.27 [128.51-903.94] mg·h/dL vs. 677.05 [358.03-1,234.57] mg·h/dL, P = 0.002), and mean amplitude of glycemic excursions (65.00 [18.17-117.50] vs. 97.09 [53.00-166.67], P = 0.010) occurred compared with no treatment. CONCLUSIONS: Acarbose reduced excessive blood glucose fluctuations.