Pharmacokinetic modelling suggests that sugammadex may interact with endogenous progesterone and reduce levels by 34% in patients taking hormonal contraception. Due to this potential interaction that ...may be equivalent to missing one dose of an oral contraceptive pill, both the manufacturer and professional anaesthesia organisations recommend counselling patients to use additional non-hormonal contraception after administration of sugammadex. We performed a prospective observational study examining the changes in serum oestrogen and progesterone concentrations in premenopausal adult women undergoing an operative procedure. Sixty participants who were on hormonal contraception received sugammadex. Two additional control groups were recruited, consisting of 30 participants who were not on hormonal contraception and did not receive sugammadex, and 32 who were not on hormonal contraception and did receive sugammadex. Three blood samples were taken: before sugammadex; 15 min post-sugammadex; and 240 min post-sugammadex or end of operating theatre time. Median oestrogen levels decreased from baseline by around 40% at 240 min in all three groups (p ≤ 0.001). Progesterone levels rose significantly at 15 min (p = 0.002) in patients on contraception then decreased non-significantly to 20% below baseline at 240 min. The decrease in oestrogen and the rise in progesterone could both act to minimise the risk of ovulation and thus protect contraception in this population. We found no evidence of a change in hormone levels that might threaten contraceptive efficacy in women on hormonal contraception receiving sugammadex.
Melanocortin-2 receptor accessory protein (MRAP) has an unusual dual topology and influences the expression, localisation, signalling and internalisation of the melanocortin receptor 2 (MC2); the ...adrenocorticotropic hormone (ACTH) receptor. Mutations in MRAP are associated with familial glucocorticoid deficiency type-2 and evidence is emerging of the importance of MRAP in adrenal development and ACTH signalling. Human MRAP has two functional splice variants: MRAP-α and MRAP-β, unlike MRAP-β, MRAP-α has little expression in brain but is highly expressed in ovary. MRAP2, identified through whole human genome sequence analysis, has approximately 40% sequence homology to MRAP. MRAP2 facilitates MC2 localisation to the cell surface but not ACTH signalling. MRAP and MRAP2 have been found to regulate the surface expression and signalling of all melanocortin receptors (MC1-5). Additionally, MRAP2 moderates the signalling of the G-protein coupled receptors (GCPRs): orexin, prokineticin and GHSR1a; the ghrelin receptor.
Whilst MRAP appears to be mainly involved in glucocorticoid synthesis, an important role is emerging for MRAP2 in regulating appetite and energy homeostasis. Transgenic models indicate the importance of MRAP in adrenal gland formation. Like MC3R and MC4R knockout mice, MRAP2 knockout mice have an obese phenotype. In vitro studies indicate that MRAP2 enhances the MC3 and MC4 response to the agonist αMSH, which, like ACTH, is produced through precursor polypeptide proopiomelanocortin (POMC) cleavage. Analysis of cohorts of individuals with obesity have revealed several MRAP2 genetic variants with loss of function mutations which are causative of monogenic hyperphagic obesity with hyperglycaemia and hypertension. MRAP2 may also be associated with female infertility. This review summarises current knowledge of MRAP and MRAP2, their influence on GPCR signalling, and focusses on pathophysiology, particularly familial glucocorticoid deficiency type-2 and obesity.
The study of J/ψ photoproduction at low energies has consequences for the understanding of multiple aspects of nonperturbative QCD, ranging from mechanical properties of the proton to the binding ...inside nuclei and the existence of hidden-charm pentaquarks. Factorization of the photon-c$\overline{c}$ and nucleon dynamics or vector meson dominance are often invoked to justify these studies. Alternatively, open-charm intermediate states have been proposed as the dominant mechanism underlying J/ψ photoproduction. As the latter violates this factorization, it is important to estimate the relevance of such contributions. We analyze the latest differential and integrated photoproduction cross sections from the GlueX and J/ψ - 007 experiments. We show that the data can be adequately described by a small number of partial waves, which we parametrize with generic models enforcing low-energy unitarity. The results suggest a non-negligible contribution from open-charm intermediate states. Furthermore, most of the models present an elastic scattering length incompatible with previous extractions based on vector meson dominance and thus call into question its applicability to heavy mesons. Our results indicate a wide array of physics possibilities that are compatible with present data and need to be disentangled.
The Ultraviolet/Optical Telescope (UVOT) is one of three instruments onboard the Swift observatory. The photometric calibration has been published, and this paper follows up with details on other ...aspects of the calibration including a measurement of the point spread function with an assessment of the orbital variation and the effect on photometry. A correction for large-scale variations in sensitivity over the field of view is described, as well as a model of the coincidence loss which is used to assess the coincidence correction in extended regions. We have provided a correction for the detector distortion and measured the resulting internal astrometric accuracy of the UVOT, also giving the absolute accuracy with respect to the International Celestial Reference System. We have compiled statistics on the background count rates, and discuss the sources of the background, including instrumental scattered light. In each case, we describe any impact on UVOT measurements, whether any correction is applied in the standard pipeline data processing or whether further steps are recommended.
We present the discovery of PS18kh, a tidal disruption event discovered at the center of SDSS J075654.53+341543.6 (d 322 Mpc) by the Pan-STARRS Survey for Transients. Our data set includes ...pre-discovery survey data from Pan-STARRS, the All-sky Automated Survey for Supernovae, and the Asteroid Terrestrial-impact Last Alert System as well as high-cadence, multiwavelength follow-up data from ground-based telescopes and Swift, spanning from 56 days before peak light until 75 days after. The optical/UV emission from PS18kh is well-fit as a blackbody with temperatures ranging from T 12,000 K to T 25,000 K and it peaked at a luminosity of L 8.8 × 1043 erg s−1. PS18kh radiated E = (3.45 0.22) × 1050 erg over the period of observation, with (1.42 0.20) × 1050 erg being released during the rise to peak. Spectra of PS18kh show a changing, boxy/double-peaked H emission feature, which becomes more prominent over time. We use models of non-axisymmetric accretion disks to describe the profile of the H line and its evolution. We find that at early times the high accretion rate leads the disk to emit a wind which modifies the shape of the line profile and makes it bell-shaped. At late times, the wind becomes optically thin, allowing the non-axisymmetric perturbations to show up in the line profile. The line-emitting portion of the disk extends from rin ∼ 60rg to an outer radius of rout ∼ 1400rg and the perturbations can be represented either as an eccentricity in the outer rings of the disk or as a spiral arm in the inner disk.
The European Commission announced in 2008 that a fundamental revision of the medical device directives is being considered in order to clarify and strengthen the current legal framework. The system ...for testing and approving devices in Europe was established >20 years ago as a 'New Approach' to a previously little-regulated industry. It is recognized by many that the regulatory system has not kept pace with technological advances and changing patterns of medical practice. New legislation will be drafted during 2011, but medical experts have been little involved in this important process. This context makes it an opportune time for a professional association to advise from both clinical and academic perspectives about changes which should be made to improve the safety and efficacy of devices used in clinical practice and to develop more appropriate systems for their clinical evaluation and post-marketing surveillance. This report summarizes how medical devices are regulated and it reviews some serious clinical problems that have occurred with cardiovascular devices. Finally, it presents the main recommendations from a Policy Conference on the Clinical Evaluation of Cardiovascular Devices that was held at the European Heart House in January 2011.
Changes in instrumentation and data availability have caused time‐varying biases in estimates of global and regional average sea surface temperature. The size of the biases arising from these changes ...are estimated and their uncertainties evaluated. The estimated biases and their associated uncertainties are largest during the period immediately following the Second World War, reflecting the rapid and incompletely documented changes in shipping and data availability at the time. Adjustments have been applied to reduce these effects in gridded data sets of sea surface temperature and the results are presented as a set of interchangeable realizations. Uncertainties of estimated trends in global and regional average sea surface temperature due to bias adjustments since the Second World War are found to be larger than uncertainties arising from the choice of analysis technique, indicating that this is an important source of uncertainty in analyses of historical sea surface temperatures. Despite this, trends over the twentieth century remain qualitatively consistent.
Key Points
There are biases in SST measurements throughout the record
These biases have been adjusted for, but large uncertainties remain
A new SST data set, HadSST3, is presented
Since 1991, public acceptance of gays and lesbians has grown dramatically. We use two approaches to examine changing attitudes in U.S. survey data. First, we conduct cohort analyses showing that both ...generational replacement and period effects are having impacts. Since 1991, older, less accepting generations of Americans have been dying and being replaced by younger, more tolerant Americans, and all age groups have been becoming more tolerant. Second, we pool cross-sectional, time series survey data to show that there has been a broad, dramatic increase in virtually every group's acceptance of gays and lesbians over time.
Key message
The pleiotropic SNPs/haplotypes, overlapping genes (metal ion binding, photosynthesis), and homozygous/biallelic SNPs and transcription factors (HTH myb-type and BHLH) hold great ...potential for improving wheat yield potential on sodic-dispersive soils.
Sodic-dispersive soils have multiple subsoil constraints including poor soil structure, alkaline pH and subsoil toxic elemental ion concentration, affecting growth and development in wheat. Tolerance is required at all developmental stages to enhance wheat yield potential on such soils. An in-depth investigation of genome-wide associations was conducted using a field phenotypic data of 206 diverse Focused Identification of Germplasm Strategy (FIGS) wheat lines for two consecutive years from different sodic and non-sodic plots and the exome targeted genotyping by sequencing (tGBS) assay. A total of 39 quantitative trait SNPs (QTSs), including 18 haplotypes were identified on chromosome 1A, 1B, 1D, 2A, 2B, 2D, 3A, 3B, 5A, 5D, 6B, 7A, 7B, 7D for yield and yield-components tolerance. Among these, three QTSs had common associations for multiple traits, indicating pleiotropism and four QTSs had close associations for multiple traits, within 32.38 Mb. The overlapping metal ion binding (Mn, Ca, Zn and Al) and photosynthesis genes and transcription factors (PHD-, Dof-, HTH myb-, BHLH-, PDZ_6-domain) identified are known to be highly regulated during germination, maximum stem elongation, anthesis, and grain development stages. The homozygous/biallelic SNPs having allele frequency above 30% were identified for yield and crop establishment/plants m
−2
. These SNPs correspond to HTH myb-type and BHLH transcription factors, brassinosteroid signalling pathway, kinase activity, ATP and chitin binding activity. These resources are valuable in haplotype-based breeding and genome editing to improve yield potential on sodic-dispersive soils.
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