The curious case of the hypothalamic-pituitary-gonadal axis dysfunction in subordinate female naked mole-rats (Heterocephalus glaber): No apparent role of opioids and glucocorticoids.

The naked mole-rat (Heterocephalus glaber) is a unique model mammal in which to study socially induced inhibition of the hypothalamic-pituitary-gonadal (HPG) axis. Naked mole-rat groups exhibit a high degree of reproductive bias in which breeding is restricted to one female (the queen) and one male, with subordinate non-breeding colony members rarely, if ever, having the opportunity to reproduce due to a dysfunctional HPG axis. It is posited that aggression directed at subordinates by the queen suppresses reproduction in these subordinates, yet the underlying physiological mechanisms causing this dysfunction are unknown. This study aimed to investigate the possible factors contributing to the dysfunction of the HPG axis in subordinate female naked mole-rats with a specific focus on the role of ovarian feedback and stress-related factors such as circulating glucocorticoid and endogenous opioid peptides. The results showed that stress-related factors appear to not mediate the suppression of reproductive function in subordinate female naked mole rats. Indeed, in some cases, the activation of the stress axis may lead to reproductive activation instead of deactivation. At the same time, the role of ovarian sex steroid feedback in reproductive suppression is likely limited and not clearly delineated. This study highlights the need for detailed studies to elucidate the mechanism of reproductive suppression in this unique model mammalian species which may shed light on, and reveal novel mechanisms, in the social regulation of reproduction.

Profile and management of acute coronary syndromes at primary- and secondary-level healthcare facilities in Cape Town.

BACKGROUND: Little is known about the clinical profile and management of patients with acute coronary syndromes (ACS) in the South African public sector. METHODS: We conducted a retrospective study of patients presenting with ACS to a secondary-level healthcare facility in Cape Town during a one-year period to study the clinical profile and management of these patients. RESULTS: Among the 214 patients in this cohort, 48 (27.5%) had ST-segment elevation myocardial infarction (STEMI), 43 (24.7%) had non-ST-segment elevation myocardial infarction and 83 (47.7%) unstable angina pectoris. We identified high rates of >12-hour delays in first medical contact after symptom onset (46%) and inaccurate ECG diagnosis of STEMI (29.2%), which were associated with low rates of thrombolysis (39.6%). High rates of non-adherence and ACS recurrence were also observed. CONCLUSION: To address the local challenges in ACS management highlighted in this study, we propose the development of a regional referral network prioritising access to expedited care and primary reperfusion interventions in ACS.

The contribution of global aviation to anthropogenic climate forcing for 2000 to 2018.

Global aviation operations contribute to anthropogenic climate change via a complex set of processes that lead to a net surface warming. Of importance are aviation emissions of carbon dioxide (CO2), nitrogen oxides (NOx), water vapor, soot and sulfate aerosols, and increased cloudiness due to contrail formation. Aviation grew strongly over the past decades (1960-2018) in terms of activity, with revenue passenger kilometers increasing from 109 to 8269 billion km yr-1, and in terms of climate change impacts, with CO2 emissions increasing by a factor of 6.8 to 1034 Tg CO2 yr-1. Over the period 2013-2018, the growth rates in both terms show a marked increase. Here, we present a new comprehensive and quantitative approach for evaluating aviation climate forcing terms. Both radiative forcing (RF) and effective radiative forcing (ERF) terms and their sums are calculated for the years 2000-2018. Contrail cirrus, consisting of linear contrails and the cirrus cloudiness arising from them, yields the largest positive net (warming) ERF term followed by CO2 and NOx emissions. The formation and emission of sulfate aerosol yields a negative (cooling) term. The mean contrail cirrus ERF/RF ratio of 0.42 indicates that contrail cirrus is less effective in surface warming than other terms. For 2018 the net aviation ERF is +100.9 milliwatts (mW) m-2 (5-95% likelihood range of (55, 145)) with major contributions from contrail cirrus (57.4 mW m-2), CO2 (34.3 mW m-2), and NOx (17.5 mW m-2). Non-CO2 terms sum to yield a net positive (warming) ERF that accounts for more than half (66%) of the aviation net ERF in 2018. Using normalization to aviation fuel use, the contribution of global aviation in 2011 was calculated to be 3.5 (4.0, 3.4) % of the net anthropogenic ERF of 2290 (1130, 3330) mW m-2. Uncertainty distributions (5%, 95%) show that non-CO2 forcing terms contribute about 8 times more than CO2 to the uncertainty in the aviation net ERF in 2018. The best estimates of the ERFs from aviation aerosol-cloud interactions for soot and sulfate remain undetermined. CO2-warming-equivalent emissions based on global warming potentials (GWP* method) indicate that aviation emissions are currently warming the climate at approximately three times the rate of that associated with aviation CO2 emissions alone. CO2 and NOx aviation emissions and cloud effects remain a continued focus of anthropogenic climate change research and policy discussions.

Low loss Ge-on-Si waveguides operating in the 8-14 µm atmospheric transmission window.

Germanium-on-silicon waveguides were modeled, fabricated and characterized at wavelengths ranging from 7.5 to 11 µm. Measured waveguide losses are below 5 dB/cm for both TE and TM polarization and reach values of ∼ 1 dB/cm for ≥ 10 µm wavelengths for the TE polarization. This work demonstrates experimentally for the first time that Ge-on-Si is a viable waveguide platform for sensing in the molecular fingerprint spectral region. Detailed modeling and analysis is presented to identify the various loss contributions, showing that with practical techniques losses below 1 dB/cm could be achieved across the full measurement range.

Implications of possible interpretations of 'greenhouse gas balance' in the Paris Agreement.

The main goal of the Paris Agreement as stated in Article 2 is 'holding the increase in the global average temperature to well below 2°C above pre-industrial levels and pursuing efforts to limit the temperature increase to 1.5°C'. Article 4 points to this long-term goal and the need to achieve 'balance between anthropogenic emissions by sources and removals by sinks of greenhouse gases'. This statement on 'greenhouse gas balance' is subject to interpretation, and clarifications are needed to make it operational for national and international climate policies. We study possible interpretations from a scientific perspective and analyse their climatic implications. We clarify how the implications for individual gases depend on the metrics used to relate them. We show that the way in which balance is interpreted, achieved and maintained influences temperature outcomes. Achieving and maintaining net-zero CO2-equivalent emissions conventionally calculated using GWP100 (100-year global warming potential) and including substantial positive contributions from short-lived climate-forcing agents such as methane would result in a sustained decline in global temperature. A modified approach to the use of GWP100 (that equates constant emissions of short-lived climate forcers with zero sustained emission of CO2) results in global temperatures remaining approximately constant once net-zero CO2-equivalent emissions are achieved and maintained. Our paper provides policymakers with an overview of issues and choices that are important to determine which approach is most appropriate in the context of the Paris Agreement.This article is part of the theme issue 'The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.

Stimulation of growth hormone by kisspeptin antagonists in ewes.

Kisspeptin signalling is indispensable for fertility, stimulating gonadotropin-releasing hormone (GnRH) secretion and mediating gonadal steroid feedback on GnRH neurons. Moreover, kisspeptin neurons have been implicated in other non-reproductive neuroendocrine roles. Kisspeptin appears to also regulate growth hormone secretion but much of the data appear contradictory. We sought to clarify a potential role of kisspeptin in growth hormone (GH) regulation by examining the effect of kisspeptin antagonists on GH secretion in ewes under various physiological conditions. Our data show clear and robust increases in GH secretion following lateral ventricle or third ventricle infusion of kisspeptin antagonists p-234 and p-271 in either ovariectomized or anestrous ewes. Central infusion of kisspeptin-10 had no effect on GH secretion. To determine the level at which kisspeptin may influence GH secretion, we examined expression of the cognate kisspeptin receptor, GPR54, in pituitary cells and showed by immunocytochemistry that the majority of somatotropes express GPR54 while expression was largely negative in other pituitary cells. Overall, we have demonstrated that blocking kisspeptin signalling by antagonists stimulates GH secretion in ewes and that this is likely mediated by inhibiting endogenous kisspeptin activation of GPR54 expressed on somatotropes. The findings suggest that endogenous kisspeptin inhibits GH secretion through GPR54 expressed on somatotropes.

Constraints on global temperature target overshoot.

In the aftermath of the Paris Agreement, the climate science and policy communities are beginning to assess the feasibility and potential benefits of limiting global warming to 1.5 °C or 2 °C above preindustrial. Understanding the dependence of the magnitude and duration of possible temporary exceedance (i.e., "overshoot") of temperature targets on sustainable energy decarbonization futures and carbon dioxide (CO2) removal rates will be an important contribution to this policy discussion. Drawing upon results from the mitigation literature and the IPCC Working Group 3 (WG3) scenario database, we examine the global mean temperature implications of differing, independent pathways for the decarbonization of global energy supply and the implementation of negative emissions technologies. We find that within the scope of scenarios broadly-consistent with the WG3 database, the magnitude of temperature overshoot is more sensitive to the rate of decarbonization. However, limiting the duration of overshoot to less than two centuries requires ambitious deployment of both decarbonization and negative emissions technology. The dependencies of temperature target overshoot's properties upon currently untested negative emissions technologies suggests that it will be important to consider how climate impacts depend on both the magnitude and duration of overshoot, not just long term residual warming.

Mid-infrared light emission > 3 µm wavelength from tensile strained GeSn microdisks.

GeSn alloys with Sn contents of 8.4 % and 10.7 % are grown pseudomorphically on Ge buffers on Si (001) substrates. The alloys as-grown are compressively strained, and therefore indirect bandgap. Undercut GeSn on Ge microdisk structures are fabricated and strained by silicon nitride stressor layers, which leads to tensile strain in the alloys, and direct bandgap photoluminescence in the 3-5 µm gas sensing window of the electromagnetic spectrum. The use of pseudomorphic layers and external stress mitigates the need for plastic deformation to obtain direct bandgap alloys. It is demonstrated, that the optically pumped light emission overlaps with the methane absorption lines, suggesting that GeSn alloys are well suited for mid-infrared integrated gas sensors on Si chips.

In vitro and in vivo effects of kisspeptin antagonists p234, p271, p354, and p356 on GPR54 activation.

Kisspeptins (KPs) and their receptor (GPR54 or KiSS1R) play a key-role in regulation of the hypothalamic-pituitary-gonadal axis and are therefore interesting targets for therapeutic interventions in the field of reproductive endocrinology. As dogs show a rapid and robust LH response after the administration of KP10, they can serve as a good animal model for research concerning KP signaling. The aims of the present study were to test the antagonistic properties of KP analogs p234, p271, p354, and p356 in vitro, by determining the intracellular Ca2+ response of CHEM1 cells that stably express human GPR54, and to study the in vivo effects of these peptides on basal plasma LH concentration and the KP10-induced LH response in female dogs. Exposure of the CHEM1 cells to KP-10 resulted in a clear Ca2+ response. P234, p271, p354, and p356 did not prevent or lower the KP10-induced Ca2+ response. Moreover, the in vivo studies in the dogs showed that none of these supposed antagonists lowered the basal plasma LH concentration and none of the peptides lowered the KP10-induced LH response. In conclusion, p234, p271, p354, and p356 had no antagonistic effects in vitro nor any effect on basal and kisspeptin-stimulated plasma LH concentration in female dogs.

Sublethal effects of angling and release on golden perch Macquaria ambigua: implications for reproduction and fish health.

The present study tested the hypothesis of no delayed sublethal effects of mild angling and release on the feeding, growth, somatic condition and gonadal development of golden perch Macquaria ambigua during gametogenesis. Subsamples of adult M. ambigua (n = 17-21 of 207), originally captured from the wild and stocked into ten 0·1 ha earthen ponds, were angled and released during early and late gametogenesis. Wild samples that were concurrently collected throughout the experiment underwent rapid and synchronous gonadal development and many spawned. While no spawning occurred in the ponds, most M. ambigua underwent normal gonadal development to maturity, including the angled fish. Angled fish also fed, maintained condition and actually grew faster than non-angled captive controls. Although females that were angled during late gametogenesis more readily ingested and retained baited hooks, neither their subsequent condition nor gonadal development was significantly affected. The predominance of null results was attributed to the combined effects of the flexible reproductive strategy of M. ambigua, the benignness of mouth hooking and immediate release, and possible methodological issues arising from differential hooking success of more aggressive and resilient individuals. The findings support earlier catch-and-release research, but contrast with reports of acute reproductive effects following capture and handling for aquaculture broodstock. This discrepancy highlights the need for research to specifically address welfare questions relevant to recreational fisheries across various species and angling scenarios.

Do Hospital Boards matter for better, safer, patient care?

Manifest failings in healthcare quality and safety in many countries have focused attention on the role of hospital Boards. While a growing literature has drawn attention to the potential impacts of Board composition and Board processes, little work has yet been carried out to examine the influence of Board competencies. In this work, we first validate the structure of an established 'Board competencies' self-assessment instrument in the English NHS (the Board Self-Assessment Questionnaire, or BSAQ). This tool is then used to explore in English acute hospitals the relationships between (a) Board competencies and staff perceptions about how well their organisation deals with quality and safety issues; and (b) Board competencies and a raft of patient safety and quality measures at organisation level. National survey data from 95 hospitals (334 Board members) confirmed the factor structure of the BSAQ, validating it for use in the English NHS. Moreover, better Board competencies were correlated in consistent ways with beneficial staff attitudes to the reporting and handling of quality and safety issues (using routinely collected data from the NHS National Staff Survey). However, relationships between Board competencies and aggregate outcomes for a variety of quality and safety measures showed largely inconsistent and non-significant relationships. Overall, these data suggest that Boards may be able to impact on important staff perceptions. Further work is required to unpack the impact of Board attributes on organisational aggregate outcomes.

Effect of gonadotropin-inhibitory hormone on luteinizing hormone secretion in humans.

BACKGROUND: Gonadotropin-inhibitory hormone (GnIH, human homologue of RFRP-3) suppresses gonadotropin secretion in animal models, but its effects have not been studied in the human. OBJECTIVE: We tested the hypotheses that exogenous GnIH inhibits LH secretion (i) in postmenopausal women and (ii) in men concurrently administered exogenous kisspeptin. DESIGN: Following in vitro and in vivo preclinical studies to functionally characterize the GnIH peptide, a dose-finding study (human GnIH: 1·5-150 µg/kg/h, iv for 3 h) was undertaken, and 50 µg/kg/h selected for further evaluation. Five postmenopausal women were administered 50 µg/kg/h iv infusion for 3 h or vehicle on two separate days. Four men were administered kisspeptin-10 (0·3 µg/kg iv bolus) with simultaneous infusion of GnIH (50 µg/kg/h, iv for 3 h) or vehicle. PARTICIPANTS: Healthy postmenopausal women (mean age 58 ± 2 years, LH: 30·8 ± 2·9 IU/l, FSH: 78·7 ± 6·4 IU/l, oestradiol: <50 pmol/l) and men (39·8 ± 2·1 years, mean total testosterone 12·1 ± 1·8 nmol/l, LH 2·2 ± 0·2 IU/l). PRIMARY OUTCOME: Change in area under curve (AUC) of LH during GnIHvs vehicle. RESULTS: During GnIH administration in postmenopausal women, LH secretion decreased (ΔAUC: -9·9 ± 1·8 IU/3 h) vs vehicle (ΔAUC: -0·5 ± 1·7 IU/3 h; P = 0·02). Kisspeptin-10-stimulated LH responses in men were not affected by GnIH co-administration (60-min AUC of LH 6·2 ± 0·8 IU/h with kisspeptin-10 alone, 6·3 ± 1·0 IU/h, kisspeptin-10 with GnIH, P = 0·72). Exogenous GnIH was well tolerated, with no adverse events reported. CONCLUSIONS: Gonadotropin-inhibitory hormone decreased LH secretion in postmenopausal women in this first-in-human study. Kisspeptin-stimulated LH secretion in men was not inhibited during concomitant administration of GnIH.

An approach to the patient with a suspected tachycardia in the emergency department.

Patients present to the emergency department with either an ongoing tachycardia or a history suspicious of a tachycardia. Either way, the tachycardia needs to be documented, preferably on a 12-lead electrocardiogram (ECG) for diagnosis and management. If a tachycardiais not documented, a careful history of the palpitations should be taken to see if further monitoring and investigations are required. If a tachycardia is confirmed on an ECG, the clinician needs to classify it according to two variables: (i) regularity of the rhythm; and (ii) QRS width. This will allow a differential diagnosis to be made.

Mapping the spatio-temporal distribution of threatened batoids to improve conservation in a subtropical estuary.

The spatio-temporal distributions of four batoid species were examined in a subtropical estuary. Fluvial gradient was the most important factor explaining abundances, reflecting positive relationships with either salinity or distance from urbanised areas that were consistent across seasons and depths. The results support existing protected areas.

Analysis of Ge micro-cavities with in-plane tensile strains above 2.

Ge on Si micro-disk, ring and racetrack cavities are fabricated and strained using silicon nitride stressor layers. Photoluminescence measurements demonstrate emission at wavelengths ≥ 2.3 µm, and the highest strained samples demonstrate in-plane, tensile strains of > 2 %, as measured by Raman spectroscopy. Strain analysis of the micro-disk structures demonstrate that shear strains are present in circular cavities, which can detrimentally effect the carrier concentration for direct band transitions. The advantages and disadvantages of each type of proposed cavity structure are discussed.

A Direct Neurokinin B Projection from the Arcuate Nucleus Regulates Magnocellular Vasopressin Cells of the Supraoptic Nucleus.

Central administration of neurokinin B (NKB) agonists stimulates immediate early gene expression in the hypothalamus and increases the secretion of vasopressin from the posterior pituitary through a mechanism that depends on the activation of neurokinin receptor 3 receptors (NK3R). The present study reports that, in the rat, immunoreactivity for NK3R is expressed in magnocellular vasopressin and oxytocin neurones in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus, and that NKB immunoreactivity is expressed in fibres in close juxtaposition with vasopressin neurones at both of these sites. Retrograde tracing in the rat shows that some NKB-expressing neurones in the arcuate nucleus project to the SON and, in mice, using an anterograde tracing approach, it is found that kisspeptin-expressing neurones of the arcuate nucleus, which are known to co-express NKB, project to the SON and PVN. Finally, i.c.v. injection of the NK3R agonist senktide is shown to potently increase the electrical activity of vasopressin neurones in the SON in vivo with no significant effect detected on oxytocin neurones. The results suggest that NKB-containing neurones in the arcuate nucleus regulate the secretion of vasopressin from magnocellular neurones in rodents, and the possible significance of this is discussed.

Extending the emission wavelength of Ge nanopillars to 2.25 µm using silicon nitride stressors.

The room temperature photoluminescence from Ge nanopillars has been extended from 1.6 µm to above 2.25 µm wavelength through the application of tensile stress from silicon nitride stressors deposited by inductively-coupled-plasma plasma-enhanced chemical-vapour-deposition. Photoluminescence measurements demonstrate biaxial equivalent tensile strains of up to ∼ 1.35% in square topped nanopillars with side lengths of 200 nm. Biaxial equivalent strains of 0.9% are observed in 300 nm square top pillars, confirmed by confocal Raman spectroscopy. Finite element modelling demonstrates that an all-around stressor layer is preferable to a top only stressor, as it increases the hydrostatic component of the strain, leading to an increased shift in the band-edge and improved uniformity over top-surface only stressors layers.

Helminth parasites in the endangered Ethiopian wolf, Canis simensis.

Ethiopian wolves, Canis simensis, are an endangered carnivore endemic to the Ethiopian highlands. Although previous studies have focused on aspects of Ethiopian wolf biology, including diet, territoriality, reproduction and infectious diseases such as rabies, little is known of their helminth parasites. In the current study, faecal samples were collected from 94 wild Ethiopian wolves in the Bale Mountains of southern Ethiopia, between August 2008 and February 2010, and were screened for the presence of helminth eggs using a semi-quantitative volumetric dilution method with microscopy. We found that 66 of the 94 faecal samples (70.2%) contained eggs from at least one group of helminths, including Capillaria, Toxocara, Trichuris, ancylostomatids, Hymenolepis and taeniids. Eggs of Capillaria sp. were found most commonly, followed by Trichuris sp., ancylostomatid species and Toxocara species. Three samples contained Hymenolepis sp. eggs, which were likely artefacts from ingested prey species. Four samples contained taeniid eggs, one of which was copro-polymerase chain reaction (copro-PCR) and sequence positive for Echinococcus granulosus, suggesting a spillover from a domestic parasite cycle into this wildlife species. Associations between presence/absence of Capillaria, Toxocara and Trichuris eggs were found; and egg burdens of Toxocara and ancylostomatids were found to be associated with geographical location and sampling season.

A one-step-ahead pseudo-DIC for comparison of Bayesian state-space models.

In the context of state-space modeling, conventional usage of the deviance information criterion (DIC) evaluates the ability of the model to predict an observation at time t given the underlying state at time t. Motivated by the failure of conventional DIC to clearly choose between competing multivariate nonlinear Bayesian state-space models for coho salmon population dynamics, and the computational challenge of alternatives, this work proposes a one-step-ahead DIC, DICp, where prediction is conditional on the state at the previous time point. Simulations revealed that DICp worked well for choosing between state-space models with different process or observation equations. In contrast, conventional DIC could be grossly misleading, with a strong preference for the wrong model. This can be explained by its failure to account for inflated estimates of process error arising from the model mis-specification. DICp is not based on a true conditional likelihood, but is shown to have interpretation as a pseudo-DIC in which the compensatory behavior of the inflated process errors is eliminated. It can be easily calculated using the DIC monitors within popular BUGS software when the process and observation equations are conjugate. The improved performance of DICp is demonstrated by application to the multi-stage modeling of coho salmon abundance in Lobster Creek, Oregon.