Impact of vaginal estriol on serum hormone levels: a systematic review.

The genitourinary syndrome of menopause (GSM) affects up to 84% of postmenopausal women and may significantly reduce the quality of life in some. For symptom relief, there are several non-hormonal and hormonal vaginal products available. In Europe, vaginal estriol (E3) is the most frequently chosen estrogen for GSM treatment. The aim of this systematic review was to assess the impact of vaginal E3 on serum sex hormone levels, an outcome that has been previously used to assess safety in similar products. In our review, we did not find any alterations in serum estrone, estradiol, testosterone, progesterone and sex hormone binding globulin levels after vaginal E3 application. In contrast, some studies showed a minimal and transient decrease in serum gonadotropin levels, which however remained within the postmenopausal range. Similarly, only a few studies reported a minimal and transient increase of serum E3 levels, with the rest reporting no changes. The lack of clinically relevant long-term changes in serum sex hormone levels supports the current literature providing evidence about the safety of vaginal E3 products.

Quality of life in menopausal women in the workplace - a systematic review.

Menopausal women are a large and economically relevant group in the workforce. Yet their quality of life (QoL) and needs in the workplace have been neglected. Thus, the aim of this systematic review was to provide an overview of QoL of menopausal women in the workplace. Systematic literature searches were executed, yielding 1211 references. After abstract screening, 156 articles remained for full-text screening. Finally, 12 articles fulfilled the inclusion criteria and were included in this review. Age, educational level, type of work, working environment (e.g. crowding, confined spaces, noise, workstation design), permanent place of residency, mental factors (e.g. stress level, workload, work pattern), comorbidities, menopausal symptoms, time since menopause and physical activity have repeatedly been shown to affect QoL in the workplace in menopausal women. Low-threshold access to medical and psychological support as well as individual adaptation of the workplace environment are, among others, retrieved recommendations for employers from these findings. Further raising of awareness of special needs of menopausal working women as well as further systematic research programs are needed.

The impact of micronized progesterone on cardiovascular events - a systematic review.

Biologically identical menopausal hormone therapy (MHT) including micronized progesterone (MP) has gained much attention. We aimed to assess the impact of MP in combined MHT on venous and arterial thromboembolism (VTE/ATE) (e.g. deep venous thrombosis/pulmonary embolism, myocardial infarction [MI] and ischemic stroke). Articles were eligible if they provided endpoints regarding cardiovascular events and use of exogenous MP. Literature searches were designed and executed for the databases Medline, Embase, CINAHL, the Cochrane Library, ClinicalTrials.gov and interdisciplinary database Web of Science. Twelve studies consisting of randomized controlled trials (RCTs), case-control studies and prospective or retrospective cohort studies were included, and risk of bias was assessed. Only a minority assessed thromboembolic events as a primary endpoint, showing that in contrast to norpregnane derivatives, primary and recurrent VTE risk was not altered by combining estrogens with MP, which was also true for ischemic stroke risk. Similarly, in placebo-controlled RCTs assessing VTE/ATE as adverse events there were no significant intergroup differences. Studies on MI as a primary endpoint are missing. In conclusion, while available data suggest that MP as a component in combined MHT may have a neutral effect on the vascular system, more RCTs investigating the impact of MP alone or in combined MHT on vascular primary endpoints are needed.

Sustainability of vaginal estrogens for genitourinary syndrome of menopause - a systematic review.

Genitourinary syndrome of menopause (GSM) is a highly prevalent, not self-limiting condition displaying a major negative impact on sexual function and emotional well-being. Various non-hormonal and hormonal treatment options are available. Many women consider GSM treatment to be a short-term interval cure rather than a long-term or lifelong treatment. The aim of this systematic literature search was to assess the sustainability of vaginal estrogens for GSM treatment after treatment cessation. We found that objective GSM signs mostly deteriorated within approximately 4 weeks after vaginal estrogen treatment cessation, while vaginal estrogens had a more sustainable impact on subjective GSM symptoms up to 3-6 months. However, overall, scientific evidence on sustainability of vaginal estrogens was low. Thus, GSM treatment should not be considered a short-term interval cure but long-term therapy. Further studies in an internationally harmonized setting (Core Outcomes in Menopause [COMMA]) are needed.

Muon Creation in Supernova Matter Facilitates Neutrino-Driven Explosions.

Muons can be created in nascent neutron stars (NSs) due to the high electron chemical potentials and the high temperatures. Because of their relatively lower abundance compared to electrons, their role has so far been ignored in numerical simulations of stellar core collapse and NS formation. However, the appearance of muons softens the NS equation of state, triggers faster NS contraction, and thus leads to higher luminosities and mean energies of the emitted neutrinos. This strengthens the postshock heating by neutrinos and can facilitate explosions by the neutrino-driven mechanism.

Precision Mass Measurements of

Masses adjacent to the classical waiting-point nuclide ^{130}Cd have been measured by using the Penning-trap spectrometer ISOLTRAP at ISOLDE/CERN. We find a significant deviation of over 400 keV from earlier values evaluated by using nuclear beta-decay data. The new measurements show the reduction of the N=82 shell gap below the doubly magic ^{132}Sn. The nucleosynthesis associated with the ejected wind from type-II supernovae as well as from compact object binary mergers is studied, by using state-of-the-art hydrodynamic simulations. We find a consistent and direct impact of the newly measured masses on the calculated abundances in the A=128-132 region and a reduction of the uncertainties from the precision mass input data.

Prompt merger collapse and the maximum mass of neutron stars.

We perform hydrodynamical simulations of neutron-star mergers for a large sample of temperature-dependent nuclear equations of state and determine the threshold mass above which the merger remnant promptly collapses to form a black hole. We find that, depending on the equation of state, the threshold mass is larger than the maximum mass of a nonrotating star in isolation by between 30 and 70 percent. Our simulations also show that the ratio between the threshold mass and maximum mass is tightly correlated with the compactness of the nonrotating maximum-mass configuration. We speculate on how this relation can be used to derive constraints on neutron-star properties from future observations.

New fission fragment distributions and r-process origin of the rare-earth elements.

Neutron star (NS) merger ejecta offer a viable site for the production of heavy r-process elements with nuclear mass numbers A≳140. The crucial role of fission recycling is responsible for the robustness of this site against many astrophysical uncertainties, but calculations sensitively depend on nuclear physics. In particular, the fission fragment yields determine the creation of 110≲A≲170 nuclei. Here, we apply a new scission-point model, called SPY, to derive the fission fragment distribution (FFD) of all relevant neutron-rich, fissioning nuclei. The model predicts a doubly asymmetric FFD in the abundant A≃278 mass region that is responsible for the final recycling of the fissioning material. Using ejecta conditions based on relativistic NS merger calculations, we show that this specific FFD leads to a production of the A≃165 rare-earth peak that is nicely compatible with the abundance patterns in the Sun and metal-poor stars. This new finding further strengthens the case of NS mergers as possible dominant origin of r nuclei with A≳140.

Measuring neutron-star properties via gravitational waves from neutron-star mergers.

We demonstrate by a large set of merger simulations for symmetric binary neutron stars (NSs) that there is a tight correlation between the frequency peak of the postmerger gravitational-wave (GW) emission and the physical properties of the nuclear equation of state (EoS), e.g., expressed by the radius of the maximum-mass Tolman-Oppenheimer-Volkhoff configuration. Therefore, a single measurement of the peak frequency of the postmerger GW signal will constrain the NS EoS significantly. For optimistic merger-rate estimates a corresponding detection with Advanced LIGO is expected to happen within an operation time of roughly a year.

The unusual γ-ray burst GRB 101225A from a helium star/neutron star merger at redshift 0.33.

Long γ-ray bursts (GRBs) are the most dramatic examples of massive stellar deaths, often associated with supernovae. They release ultra-relativistic jets, which produce non-thermal emission through synchrotron radiation as they interact with the surrounding medium. Here we report observations of the unusual GRB 101225A. Its γ-ray emission was exceptionally long-lived and was followed by a bright X-ray transient with a hot thermal component and an unusual optical counterpart. During the first 10 days, the optical emission evolved as an expanding, cooling black body, after which an additional component, consistent with a faint supernova, emerged. We estimate its redshift to be z = 0.33 by fitting the spectral-energy distribution and light curve of the optical emission with a GRB-supernova template. Deep optical observations may have revealed a faint, unresolved host galaxy. Our proposed progenitor is a merger of a helium star with a neutron star that underwent a common envelope phase, expelling its hydrogen envelope. The resulting explosion created a GRB-like jet which became thermalized by interacting with the dense, previously ejected material, thus creating the observed black body, until finally the emission from the supernova dominated. An alternative explanation is a minor body falling onto a neutron star in the Galaxy.

Neutrino signal of electron-capture supernovae from core collapse to cooling.

An 8.8M{⊙} electron-capture supernova was simulated in spherical symmetry consistently from collapse through explosion to essentially complete deleptonization of the forming neutron star. The evolution time (∼9 s) is short because high-density effects suppress our neutrino opacities. After a short phase of accretion-enhanced luminosities (∼200 ms), luminosity equipartition among all species becomes almost perfect and the spectra of ν{e} and ν{µ,τ} very similar, ruling out the neutrino-driven wind as r-process site. We also discuss consequences for neutrino flavor oscillations.

Mass ejection by strange star mergers and observational implications.

We determine the Galactic production rate of strangelets as a canonical input to calculations of the measurable cosmic ray flux of strangelets by performing simulations of strange star mergers and combining the results with recent estimates of stellar binary populations. We find that the flux depends sensitively on the bag constant of the MIT bag model of QCD and disappears for high values of the bag constant and thus more compact strange stars. In the latter case, strange stars could coexist with ordinary neutron stars as they are not converted by the capture of cosmic ray strangelets. An unambiguous detection of an ordinary neutron star would then not rule out the strange matter hypothesis.

Insulin therapy in elderly patients with type 2 diabetes: the role of insulin glargine.

Within the USA, between 1980 and 2005, the prevalence of diagnosed diabetes has increased in all age groups, with the age group 65-74 years having the highest prevalence. The treatment of type 2 diabetes mellitus (T2DM) in elderly people is made more difficult than in their younger counterparts, primarily owing to the impact of co-morbidities, complications and hypoglycaemia as well as technical difficulties with insulin injections. Accordingly, the treatment approach for elderly patients with T2DM may need to be modified to accommodate co-morbidities and illnesses associated with ageing. Risks associated with insulin therapy, particularly hypoglycaemia, have traditionally limited the use of insulin in this patient population. Insulin glargine is associated with a low risk of hypoglycaemia compared with neutral protamine Hagedorn insulin, for example, and could thus provide a treatment of choice for healthcare providers when considering the increasing prevalence of diabetes in the elderly population. A regimen based on insulin glargine plus oral agents provides clinicians with a tool to help meet therapeutic targets in this population without increasing risk of hypoglycaemia.

Effects of inelastic neutrino-nucleus scattering on supernova dynamics and radiated neutrino spectra.

Based on the shell model for Gamow-Teller and the random phase approximation for forbidden transitions, we calculate cross sections for inelastic neutrino-nucleus scattering (INNS) under supernova (SN) conditions, assuming a matter composition given by nuclear statistical equilibrium. The cross sections are incorporated into state-of-the-art stellar core-collapse simulations with detailed energy-dependent neutrino transport. While no significant effect on the SN dynamics is observed, INNS increases the neutrino opacities noticeably and strongly reduces the high-energy tail of the neutrino spectrum emitted in the neutrino burst at shock breakout. Relatedly the expected event rates for the observation of such neutrinos by earthbound detectors are reduced by up to about 60%.

Gravitational waves from relativistic neutron-star mergers with microphysical equations of state.

The gravitational wave (GW) emission from a set of relativistic neutron-star (NS) merger simulations is analyzed and characteristic signal features are identified. The distinct peak in the GW energy spectrum that is associated with the formation of a hypermassive merger remnant has a frequency that depends strongly on the properties of the nuclear equation of state (EOS) and on the total mass of the binary system, whereas the mass ratio and the NS spins have a weak influence. If the total mass can be determined from the inspiral chirp signal, the peak frequency of the post-merger signal is a sensitive indicator of the EOS.

Generic gravitational-wave signals from the collapse of rotating stellar cores.

We perform general relativistic (GR) simulations of stellar core collapse to a protoneutron star, using a microphysical equation of state (EOS) and an approximation of deleptonization. We show that for a wide range of rotation rates and profiles the gravitational-wave (GW) burst signals from the core bounce are generic, known as type I. In our systematic study, using both GR and Newtonian gravity, we identify and quantify the influence of rotation, the EOS, and deleptonization on this result. Such a generic type of signal templates will facilitate a more efficient search in current and future GW detectors of both interferometric and resonant type.

3D collapse of rotating stellar iron cores in general relativity including deleptonization and a nuclear equation of state.

We present 2D and 3D simulations of the collapse of rotating stellar iron cores in general relativity employing a nuclear equation of state and an approximate treatment of deleptonization. We compare fully general relativistic and conformally flat evolutions and find that the latter treatment is sufficiently accurate for the core-collapse supernova problem. We focus on gravitational wave (GW) emission from rotating collapse, bounce, and early postbounce phases. Our results indicate that the GW signature of these phases is much more generic than previously estimated. We also track the growth of a nonaxisymmetric instability in one model, leading to strong narrow-band GW emission.

Insulin glargine added to therapy with oral antidiabetic agents improves glycemic control and reduces long-term complications in patients with type 2 diabetes - a simulation with the Diabetes Mellitus Model (DMM).

OBJECTIVE: The purpose of this study was to compare the effect of two insulin therapies with respect to long-term complications in type 2 diabetes patients using the Diabetes Mellitus Model (DMM). The therapies under investigation were insulin glargine combined with the oral antidiabetic agents, glimepiride and metformin, (BOT = basal supported oral treatment) and premixed insulin (CT = conventional therapy). METHODS: The DMM predicts complications over a 10-year period using data from published studies. Particular interest is placed on the influence of HbA1c levels related to time. The simulations are based on 10,000 virtual patients taking BOT and CT and the clinical data are based on the results of the LAPTOP study (Lantus + Amaryl + metformin versus premixed insulin in patients with type 2 diabetes mellitus after failing oral treatment pathways) comparing BOT and CT for 24 weeks. The simulations were performed in patients aged 60 A+/- 9 years with type 2 diabetes in which the duration of disease had a baseline of 9 A+/- 7 years. Sensitivity analyses were carried out by changing the response rate of those on BOT, the age of patients and duration of diabetes. RESULTS: The overall relative risk reductions obtained with BOT versus CT for the base case are, 11% for the nervous and vascular systems, 7% for the renal system, 5% for ophthalmic disorders, 3% for the cardiovascular system and mortality and 6% for any kind of event after 10 years. The advantages of BOT were robust to all the changes in the sensitivity analyses. When compared with the base case, the best therapeutic effects were obtained in younger patients who had been diabetic for a shorter period. CONCLUSIONS: Using the DMM data from the LAPTOP study, simulations based on both therapies showed that the BOT regimen provides better glycemic control and reduction in HbA1c thereby leading to a reduction in the long-term complications of diabetes and mortality.

C-reactive protein is a strong independent predictor of death in type 2 diabetes: association with multiple facets of the metabolic syndrome.

INTRODUCTION: It has been suggested that atherosclerotic vascular disease is a chronic inflammatory process. The aim of this study was to investigate the importance of C-reactive protein (CRP) as a cardiovascular risk marker and predictor of death, as well as its relation to other factors of the metabolic syndrome in a cohort of type 2 diabetic patients at high risk of severe macrovascular complications. MATERIAL AND METHODS: 592 patients, aged 55 to 74 years (311 men, 281 women), with signs and symptoms of circulation deficits were examined by duplex ultrasound for suspected cerebrovascular and peripheral arterial disease and followed over a period of 5 years. At baseline, 292 patients of the total group had type 2 diabetes (49.3%). Ischemic heart disease was present in 40.2%, internal carotid stenosis in 21.9% and peripheral arterial disease in 39.7% of the subjects. RESULTS: During the observation period, 104 patients had died, 72 (69.2%) due to cardiovascular causes. Non-fatal myocardial infarction occurred in 39 patients (7.4%), non-fatal stroke in 70 patients (13.3%) and amputations because of gangrene were unavoidable in 24 patients (4.6%). In Cox regression analysis, CRP was the strongest predictor of death and cardiovascular death in the total cohort (RR 3.7 [95% CI 1.86-7.50] and 5.4 [2.13-13.76]), as well as in the type 2 diabetic subgroup (RR 3.3 [1.27-8.70] and 5.4 [1.44-20.0]). In contrast neither the traditional cardiovascular risk factors nor the data of diabetic metabolic control were able to improve prediction. CRP was correlated positively with plasma levels of triglycerides (r=0.19, p=0.002), C-peptide (r=0.21, p=0.004), postprandial glucose (r=0.17, p=0.009), albuminuria (r=0.16, p=0.020), and inversely with HDL cholesterol (r=-0.20, p=0.002) in type 2 diabetic patients. CONCLUSIONS: CRP seems to be a better predictor of death and cardiovascular events than traditional risk factors or parameters of metabolic control in type 2 diabetic patients at high risk for cardiovascular endpoints. Additionally, CRP is associated with several facets of the metabolic syndrome.

Pulsar recoil by large-scale anisotropies in supernova explosions.

Assuming that the neutrino luminosity from the neutron star core is sufficiently high to drive supernova explosions by the neutrino-heating mechanism, we show that low-mode (l=1,2) convection can develop from random seed perturbations behind the shock. A slow onset of the explosion is crucial, requiring the core luminosity to vary slowly with time, in contrast to the burstlike exponential decay assumed in previous work. Gravitational and hydrodynamic forces by the globally asymmetric supernova ejecta were found to accelerate the remnant neutron star on a time scale of more than a second to velocities above 500 km s(-1), in agreement with observed pulsar proper motions.