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Although many animals deposit scent marks, previous studies have focused almost entirely on rodents or on the chemical structure of the signal. Here, we study the quantity and temporal pattern of chemical deposition by the territorial sagebrush lizard Sceloporus graciosus, measuring both femoral pore and fecal deposits. Specifically, we tested whether variation in deposition is a good cue of individual and sexual identity and/or whether it is more closely associated with body size and reproductive state, indicators of physiological condition. The results support the latter hypothesis. We found that although the amount of fluid deposited on a single perch (rarely quantified in mammals) carries little information on individual or sexual identity, it reflects the physiological condition and reproductive state of individual lizards and is replenished on a roughly weekly cycle, potentially providing additional information on the producer's activity level. The amount of deposition may thus provide important information to chemical receivers making mate choice and territorial defense decisions. The results further suggest that seasonal increases in gland production allow lizards to mark more sites rather than to influence the quality of the signal on a single perch. [ABSTRACT FROM AUTHOR]

This cross-sectional study aimed to explore the incidence of impostor phenomenon among 79 nurses in specialist roles in a single NHS trust in England, using an online anonymous questionnaire that included the Clance Imposter Phenomenon Scale and free-text responses. Results indicated a high prevalence of impostor phenomenon, with no specific variables predicting its occurrence. Four main themes emerged: self-doubt, role expectations, fear of exposure as an impostor, and factors leading to burnout. The study highlights the need for targeted support and training for this cohort, particularly as impostor phenomenon was found to be prevalent during career transitions and was not limited by gender. The findings have implications for nursing management and education, offering the opportunity to develop specific support mechanisms to alleviate impostor phenomenon and potentially reduce attrition rates in specialist nursing roles.

Study Question: Does trophectoderm biopsy (TEBx) of blastocysts for preimplantation genetic testing in the clinic affect normal placental and embryo development and offspring metabolic outcomes in a mouse model?, Summary Answer: TEBx impacts placental and embryonic health during early development, with some alterations resolving and others worsening later in development and triggering metabolic changes in adult offspring., What Is Known Already: Previous studies have not assessed the epigenetic and morphological impacts of TEBx either in human populations or in animal models., Study Design, Size, Duration: We employed a mouse model to identify the effects of TEBx during IVF. Three groups were assessed: naturally conceived (Naturals), IVF, and IVF + TEBx, at two developmental timepoints: embryonic day (E)12.5 (n = 40/Naturals, n = 36/IVF, and n = 36/IVF + TEBx) and E18.5 (n = 42/Naturals, n = 30/IVF, and n = 35/IVF + TEBx). Additionally, to mimic clinical practice, we assessed a fourth group: IVF + TEBx + Vitrification (Vit) at E12.5 (n = 29) that combines TEBx and vitrification. To assess the effect of TEBx in offspring health, we characterized a 12-week-old cohort (n = 24/Naturals, n = 25/IVF and n = 25/IVF + TEBx)., Participants/materials, Setting, Methods: Our mouse model used CF-1 females as egg donors and SJL/B6 males as sperm donors. IVF, TEBx, and vitrification were performed using standardized methods. Placenta morphology was evaluated by hematoxylin-eosin staining, in situ hybridization using Tpbpa as a junctional zone marker and immunohistochemistry using CD34 fetal endothelial cell markers. For molecular analysis of placentas and embryos, DNA methylation was analyzed using pyrosequencing, luminometric methylation assay, and chip array technology. Expression patterns were ascertained by RNA sequencing. Triglycerides, total cholesterol, high-, low-, and very low-density lipoprotein, insulin, and glucose were determined in the 12-week-old cohort using commercially available kits., Main Results and the Role of Chance: We observed that at E12.5, IVF + TEBx had a worse outcome in terms of changes in DNA methylation and differential gene expression in placentas and whole embryos compared with IVF alone and compared with Naturals. These changes were reflected in alterations in placental morphology and blood vessel density. At E18.5, early molecular changes in fetuses were maintained or exacerbated. With respect to placentas, the molecular and morphological changes, although different compared to Naturals, were equivalent to the IVF group, except for changes in blood vessel density, which persisted. Of note is that most differences were sex specific. We conclude that TEBx has more detrimental effects in mid-gestation placental and embryonic tissues, with alterations in embryonic tissues persisting or worsening in later developmental stages compared to IVF alone, and the addition of vitrification after TEBx results in more pronounced and potentially detrimental epigenetic effects: these changes are significantly different compared to Naturals. Finally, we observed that 12-week IVF + TEBx offspring, regardless of sex, showed higher glucose, insulin, triglycerides, lower total cholesterol, and lower high-density lipoprotein compared to IVF and Naturals, with only males having higher body weight compared to IVF and Naturals. Our findings in a mouse model additionally support the need for more studies to assess the impact of new procedures in ART to ensure healthy pregnancies and offspring outcomes., Large Scale Data: Data reported in this work have been deposited in the NCBI Gene Expression Omnibus under accession number GSE225318., Limitations, Reasons for Caution: This study was performed using a mouse model that mimics many clinical IVF procedures and outcomes observed in humans, where studies on early embryos are not possible., Wider Implications of the Findings: This study highlights the importance of assaying new procedures used in ART to assess their impact on placenta and embryo development, and offspring metabolic outcomes., Study Funding/competing Interest(s): This work was funded by a National Centers for Translational Research in Reproduction and Infertility grant P50 HD068157-06A1 (M.S.B., C.C., M.M.), Ruth L. Kirschstein National Service Award Individual Postdoctoral Fellowship F32 HD107914 (E.A.R.-C.) and F32 HD089623 (L.A.V.), and National Institutes of Health Training program in Cell and Molecular Biology T32 GM007229 (C.N.H.). No conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In vitro fertilization (IVF) is associated with DNA methylation abnormalities and a higher incidence of adverse pregnancy outcomes. However, which exposure(s), among the many IVF interventions, contributes to these outcomes remains unknown. Frozen embryo transfer (ET) is increasingly utilized as an alternative to fresh ET, but reports suggest a higher incidence of pre-eclampsia and large for gestational age infants. This study examines DNA methylation in human placentas using the 850K Infinium MethylationEPIC BeadChip array obtained after 65 programmed frozen ET cycles, 82 fresh ET cycles and 45 unassisted conceptions. Nine patients provided placentas following frozen and fresh ET from consecutive pregnancies for a paired subgroup analysis. In parallel, eight mouse placentas from fresh and frozen ET were analyzed using the Infinium Mouse Methylation BeadChip array. Human and mouse placentas were significantly hypermethylated after frozen ET compared with fresh. Paired analysis showed similar trends. Sex-specific analysis revealed that these changes were driven by male placentas in humans and mice. Frozen and fresh ET placentas were significantly different from controls, with frozen samples hypermethylated compared with controls driven by males and fresh samples being hypomethylated compared with controls, driven by females. Sexually dimorphic epigenetic changes could indicate differential susceptibility to IVF-associated perturbations, which highlights the importance of sex-specific evaluation of adverse outcomes. Similarities between changes in mice and humans underscore the suitability of the mouse model in evaluating how IVF impacts the epigenetic landscape, which is valuable given limited access to human tissue and the ability to isolate specific interventions in mice., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

We introduce a summary wellbeing measure for economic evaluation of cross-sectoral public policies with impacts on health and living standards. We show how to calculate period-specific and lifetime wellbeing using quality-adjusted life years based on widely available data on health-related quality of life and consumption and normative assumptions about three parameters-minimal consumption, standard consumption, and the elasticity of the marginal value of consumption. We also illustrate how these three parameters can be tailored to the decision-making context and varied in sensitivity analysis to provide information about the implications of alternative value judgments. As well as providing a general measure for cost-effectiveness analysis and cost-benefit analysis in terms of wellbeing, this approach also facilitates distributional analysis in terms of how many good years different population subgroups can expect to live under different policy scenarios., (© 2020 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Superovulation with gonadotropins alters the hormonal milieu during early embryo development and placentation, and may be responsible for fetal and placental changes observed after in vitro fertilization (IVF). We hypothesized that superovulation has differential effects depending on timing of exposure. To test our hypothesis, we isolated the effect of superovulation on pre- and peri-implantation mouse embryos. Blastocysts were obtained from either natural mating or following superovulation and mating, and were transferred into naturally mated or superovulated pseudopregnant recipient mice. Fetal weight was significantly lower after peri-implantation exposure to superovulation, regardless of preimplantation exposure (p = 0.006). Placentas derived from blastocysts exposed to superovulation pre- and peri-implantation were larger than placentas derived from natural blastocysts that are transferred into a natural or superovulated environment (p < 0.05). Fetal-to-placental weight ratio decreased following superovulation during the pre- or peri-implantation period (p = 0.05, 0.01, respectively) and these effects were additive. Peg3 DNA methylation levels were decreased in placentas derived from exposure to superovulation both pre- and peri-implantation compared with unexposed embryos and exposure of the preimplantation embryo only. Through RNA sequencing on placental tissue, changes were identified in genes involved in immune system regulation, specifically interferon signaling, which has been previously implicated in implantation and maintenance of early pregnancy in mice. Overall, we found that the timing of exposure to gonadotropin stimulation can have differential effects on fetal and placental growth. These findings could impact clinical practice and underscores the importance of dissecting the role of procedures utilized during IVF on pregnancy complications., (© The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We evaluate the total probability of human extinction from naturally occurring processes. Such processes include risks that are well characterized such as asteroid impacts and supervolcanic eruptions, as well as risks that remain unknown. Using only the information that Homo sapiens has existed at least 200,000 years, we conclude that the probability that humanity goes extinct from natural causes in any given year is almost guaranteed to be less than one in 14,000, and likely to be less than one in 87,000. Using the longer track record of survival for our entire genus Homo produces even tighter bounds, with an annual probability of natural extinction likely below one in 870,000. These bounds are unlikely to be affected by possible survivorship bias in the data, and are consistent with mammalian extinction rates, typical hominin species lifespans, the frequency of well-characterized risks, and the frequency of mass extinctions. No similar guarantee can be made for risks that our ancestors did not face, such as anthropogenic climate change or nuclear/biological warfare.

Preterm birth (PTB) affects approximately 1 in 10 pregnancies and contributes to approximately 50% of neonatal mortality. However, despite decades of research, little is understood about the etiology of PTB, likely due to the multifactorial nature of the disease. In this study, we examined preterm and term placentas, from unassisted conceptions and those conceived using in vitro fertilization (IVF). IVF increases the risk of PTB and causes epigenetic change in the placenta and fetus; therefore, we utilized these patients as a unique population with a potential common etiology. We investigated genome-wide DNA methylation in placentas from term IVF, preterm IVF, term control (unassisted conception) and preterm control pregnancies and discovered epigenetic dysregulation of multiple genes involved in cell migration, including members of the ADAMTS family, ADAMTS12 and ADAMTS16. These genes function in extracellular matrix regulation and tumor cell invasion, processes replicated by invasive trophoblasts (extravillous trophoblasts (EVTs)) during early placentation. Though expression was similar between term and preterm placentas, we found that both genes demonstrate high expression in first- and second-trimester placenta, specifically in EVTs and syncytiotrophoblasts. When we knocked down ADAMTS12 or ADAMTS16in vitro, there was poor EVT invasion and reduced matrix metalloproteinase activity, reinforcing their critical role in placentation. In conclusion, utilizing a population at high risk for PTB, we have identified a role for ADAMTS gene methylation in regulating early placentation and susceptibility to PTB.

Purpose: Epidemiologic data suggest that in vitro fertilization (IVF) is associated with an increased risk of disorders of placentation including preeclampsia and fetal growth restriction. Specifically, studies have demonstrated that singleton pregnancies conceived following a fresh embryo transfer are at an increased risk of delivering an infant with low birth weight compared to those conceived following a frozen embryo transfer. The mechanism responsible for this association remains unclear. Procedures utilized in IVF have also been linked with epigenetic changes and gene expression changes in both fetal and maternal tissues. Data suggest that modifications in the maternal endometrium can lead to disordered trophoblast invasion and placentation. This study examines the effect of ovarian stimulation on endometrial gene expression and DNA methylation during the window of implantation to examine potential pathways playing a role in the adverse outcomes associated with IVF., Methods: Endometrial biopsies were obtained from oocyte donors and age-matched naturally cycling women 11 days following oocyte retrieval in donors or 12 days following luteinizing hormone (LH) surge in naturally cycling women. Global gene expression was analyzed via Affymetrix Human Gene 1.1 ST array and confirmed with RT-qPCR. DNA methylation was assessed with the Infinium DNA methylation 450 K BeadChip., Results: Analysis of endometrial gene expression from 23 women (11 oocyte donors and 12 controls) demonstrated 165 genes with a greater than twofold change in expression between donors and controls. While there were 785 genes with significant differential methylation in the endometrium of donors when compared with control subjects, none of the genes with altered expression showed significant changes in DNA methylation. Analysis of the differentially expressed genes showed enrichment for genes involved in endometrial remodeling including PLAT, HSPE2, MMP2, and TIMP1. Validation studies using RT-qPCR found a 73% reduction in expression of heparanase 2 (HSPE2) an enzyme associated with both angiogenesis and cell invasion, a greater than twofold increase in tissue-type plasminogen activator (PLAT), a serine protease participating in matrix degradation, and a 70% increase in MMP2, a gelatinase involved in collagen and fibronectin breakdown., Conclusions: Superovulation alters expression of genes critical to endometrial remodeling during early implantation. Such changes could lead to altered trophoblast migration and impaired endovascular invasion. These findings offer a potential mechanism for the adverse perinatal outcomes observed following embryo transfer during fresh IVF cycles.

The World Bank is publishing nine volumes of Disease Control Priorities, 3rd edition (DCP3) between 2015 and 2018. Volume 9, Improving Health and Reducing Poverty, summarises the main messages from all the volumes and contains cross-cutting analyses. This Review draws on all nine volumes to convey conclusions. The analysis in DCP3 is built around 21 essential packages that were developed in the nine volumes. Each essential package addresses the concerns of a major professional community (eg, child health or surgery) and contains a mix of intersectoral policies and health-sector interventions. 71 intersectoral prevention policies were identified in total, 29 of which are priorities for early introduction. Interventions within the health sector were grouped onto five platforms (population based, community level, health centre, first-level hospital, and referral hospital). DCP3 defines a model concept of essential universal health coverage (EUHC) with 218 interventions that provides a starting point for country-specific analysis of priorities. Assuming steady-state implementation by 2030, EUHC in lower-middle-income countries would reduce premature deaths by an estimated 4·2 million per year. Estimated total costs prove substantial: about 9·1% of (current) gross national income (GNI) in low-income countries and 5·2% of GNI in lower-middle-income countries. Financing provision of continuing intervention against chronic conditions accounts for about half of estimated incremental costs. For lower-middle-income countries, the mortality reduction from implementing the EUHC can only reach about half the mortality reduction in non-communicable diseases called for by the Sustainable Development Goals. Full achievement will require increased investment or sustained intersectoral action, and actions by finance ministries to tax smoking and polluting emissions and to reduce or eliminate (often large) subsidies on fossil fuels appear of central importance. DCP3 is intended to be a model starting point for analyses at the country level, but country-specific cost structures, epidemiological needs, and national priorities will generally lead to definitions of EUHC that differ from country to country and from the model in this Review. DCP3 is particularly relevant as achievement of EUHC relies increasingly on greater domestic finance, with global developmental assistance in health focusing more on global public goods. In addition to assessing effects on mortality, DCP3 looked at outcomes of EUHC not encompassed by the disability-adjusted life-year metric and related cost-effectiveness analyses. The other objectives included financial protection (potentially better provided upstream by keeping people out of the hospital rather than downstream by paying their hospital bills for them), stillbirths averted, palliative care, contraception, and child physical and intellectual growth. The first 1000 days after conception are highly important for child development, but the next 7000 days are likewise important and often neglected., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We introduce new theoretical insights into two-population asymmetric games allowing for an elegant symmetric decomposition into two single population symmetric games. Specifically, we show how an asymmetric bimatrix game (A,B) can be decomposed into its symmetric counterparts by envisioning and investigating the payoff tables (A and B) that constitute the asymmetric game, as two independent, single population, symmetric games. We reveal several surprising formal relationships between an asymmetric two-population game and its symmetric single population counterparts, which facilitate a convenient analysis of the original asymmetric game due to the dimensionality reduction of the decomposition. The main finding reveals that if (x,y) is a Nash equilibrium of an asymmetric game (A,B), this implies that y is a Nash equilibrium of the symmetric counterpart game determined by payoff table A, and x is a Nash equilibrium of the symmetric counterpart game determined by payoff table B. Also the reverse holds and combinations of Nash equilibria of the counterpart games form Nash equilibria of the asymmetric game. We illustrate how these formal relationships aid in identifying and analysing the Nash structure of asymmetric games, by examining the evolutionary dynamics of the simpler counterpart games in several canonical examples.

Epidemiological studies suggest that babies born following in vitro fertilization (IVF) and fresh embryo transfer are of lower birthweight than babies born following frozen embryo transfer, although the mechanism responsible for this phenotype is not known. We developed a novel mouse model that isolates the independent effects of embryo freezing and the superovulated environment, which cannot be performed in humans. We transferred blastocysts that had been vitrified and warmed, mixed with with fresh blastocysts, into individual pseudopregnant recipients produced by either natural mating or mating following injection with equine chorionic gonadotropin and human chorionic gonadotropin and hCG (superovulation). We found that superovulation of the recipient dams led to significantly lower fetal weight at term while blastocyst vitrification had no significant effect on fetal weight (1.43 ± 0.24 g fresh-natural, 1.30 ± 0.28 g vitrified-natural vs. 1.09 ± 0.20 fresh-superovulated, 0.93 ± 0.23 g vitrified-superovulated, P < 0.0001). Doppler ultrasound revealed increased median umbilical artery resistance in the placentae of near-term dams exposed to superovulation compared to naturally mated dams (0.927 vs 0.904, P = 0.02). Additionally, placental microvascular density was lower in superovulated compared to naturally mated dams (1.24 × 10-3 vessel/micron vs 1.46 × 10-3 vessels/micron, P = 0.046). Gene expression profiling suggested alterations in fetal genes involved in glucorticoid regulation. These results suggest a potential mechanism for altered birthweight following superovulation in our model and may have implications for human IVF., (© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Tribbles homolog 3 (TRIB3) is a mammalian gene that is upregulated in response to several types of cell death-inducing cellular stress. The TRIB3 protein is a pseudokinase, a protein kinase-like scaffold with impaired catalytic activity. However, research has revealed it to be prolific at forming protein- protein interactions. By binding to and regulating the activity of several key proteins, including the protein kinase Akt and transcription factors ATF4, CHOP and NF-κB, TRIB3 is at a junction of several signaling pathways. This review begins by providing insights into the characteristic protein structure and gene expression regulation mechanisms of TRIB3. Further, the diverse reported molecular roles of TRIB3 as a regulator of cell death, stress responses, inflammation, cell differentiation, protein degradation and other processes are discussed. Special attention is devoted to the involvement of TRIB3 in the pathogenesis of cancer and type 2 diabetes, two fields where TRIB3 has generated particular interest, as well as considerable debate, from a biomedical standpoint. Throughout, emphasis is placed on results obtained from animal models with altered TRIB3 expression (Trib3 knockout or overexpression mice), in order to provide insight into the contributions of TRIB3 to physiology and disease at the organism level., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

While live births resulting from assisted reproductive technology (ART) exceed 1% of total births annually, the effect of ART on fetal development is not well understood. Data have demonstrated that IVF leads to alterations in DNA methylation and gene expression in the placenta that may have long-term effects on health and disease. Studies have linked adverse neurodevelopmental outcomes to ART, although human studies are inconclusive. In order to isolate the peri-implantation environment and its effects on brain development, we utilized a mouse model with and without superovulation and examined the effect of adult behavior as well as adult cortical neuronal density. Adult offspring of superovulated dams showed increased anxiety-like behavior compared to offspring of naturally mated dams (P < .05). There was no difference in memory and learning tests between the 2 groups. The adult brains from offspring of superovulated recipients had fewer neurons per field compared to naturally mated control offspring (P < .05). In order to examine potential pathways leading to these changes, we measured messenger RNA and microRNA (miRNA) expression in fetal brains at E18.5. Microarray analysis found that miRNAs miR-122, miR-144, and miR-211, involved in regulation of neuronal migration and differentiation, were downregulated in brains of offspring exposed to a superovulated environment(P < .05). There was also altered expression of genes involved in neuronal development. These results suggest that the peri-implantation environment can affect neurodevelopment and can lead to behavioral changes in adulthood. Human studies with long-term follow-up of children from ART are necessary to further investigate the influence of ART on the offspring., (© The Author(s) 2015.)