Spontaneous discrimination of urine odours in wild African lions (Panthera leo)

Olfactory communication is the primary mode of communication for many mammals, yet research on this form of signalling is still largely descriptive in most species. Thus, despite the apparent importance of scent-marking in the social lives of wild felids, experimental studies directly investigating the function of olfactory communication are lacking. We conducted scent presentation experiments to investigate whether wild African lions can discriminate another lion's social group and sex from a sample of its urine. Our results indicated that lion urine has the potential to signal depositor sex and social group, and that lions can use urine to discriminate males from females and residents from non-residents. The response of lions to urine was also dependent on both the sex and age of the subject receiving the presentation. Female lions responded less frequently to urine from resident females than to either non-resident females or resident males. Males responded more strongly to urine from resident males than resident females, but did not appear to differentiate urine from non-resident and resident females. Observations of flehmen and further scent-marking responses from lions provide additional evidence that lion urine functions in scent-marking. These results establish that urine scent-marks contain sufficient information for receivers to discriminate the sex and social affiliation of the signaller, and are the first to experimentally demonstrate the functional relevance of scent-marking in African lions

Spatial and seasonal patterns of communal latrine use by spotted hyenas (Crocuta crocuta) reflect a seasonal resource defense strategy

© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Abstract: Communal marking sites, or latrines, appear to play an important role in intraspecific communication and social dynamics in a wide range of mammal species. The spatial distribution of latrines can provide clues to their function and has been well documented in a number of species. Latrine use may vary considerably through time, however, and a more comprehensive approach to their study that considers spatial and seasonal patterns of use is required to understand more fully the costs and benefits of latrine use, and hence their adaptive significance. This study investigated spatial and seasonal patterns of latrine use by spotted hyena (Crocuta crocuta) in northern Botswana, examining their potential role in resource defense. Latrine characteristics and hyena activity were monitored to test the influence of season and location (relative to clan territories and roads) on latrine use. We conducted monthly scat counts (at 78 latrines) and continuously recorded hyena visitation (to 50 latrines) in five clan home ranges, demonstrating clear seasonal patterns in latrine use. Latrines were smaller in the wet season (November-March), resulting from fewer visits by hyenas, reduced scat accumulation, and the seasonal activity of coprophagous beetles. We speculate that such a seasonal pattern may be driven by reduced competition for food during the wet season. Latrines located within core clan areas were no larger or more frequently used than those in home-range boundary areas, but hyenas did preferentially place latrines alongside roads and were more likely to reuse road-side latrines in subsequent years. This pattern was not due to observer detection bias and adds to the growing body of literature on the impact that roads and other anthropogenic features have on the communication and movement ecology of wild animals. Significance statement: Although most mammals use communal marking sites, very little is known about their function and detailed patterns of use in many species. We investigated latrine use in spotted hyena (Crocuta crocuta) and describe spatial and temporal marking patterns that are consistent with optimizing scent longevity and detection. Spatially, hyenas preferentially located latrines along the edge of man-made vehicle tracks, which may increase signal detection and transmission. Seasonal marking patterns suggest that hyenas optimize their communication by concentrating activity in the dry season, thereby avoiding the disruptive effects of coprophagous dung beetles and rain, and focusing activity during periods when food resources are expected to be scarcer. These results demonstrate seasonal and spatial optimization of communication, including in response to novel anthropogenic features in the environment such as roads, advancing our understanding of communication strategies in mammals more broadly

Validation and Clinical Application of a New Liquid Chromatography Coupled to Mass Spectrometry (HPLC-MS) Method for Dalbavancin Quantification in Human Plasma

Dalbavancin (DBV) is an intravenous long-acting second-generation glycolipopeptide antibiotic with high efficacy and excellent tolerability, approved for use in the treatment of Gram-positive skin and skin structure infections (ABSSSI). Nevertheless, little is known about its pharmacokinetic/pharmacodynamic (PK/PD) properties in real life, which is also due to technical challenges in its quantification in human plasma, preventing an effective application of therapeutic drug monitoring (TDM). In fact, DBV has a high affinity to plasma proteins, possibly resulting in poor recovery after extraction procedure. The aim of this study was to validate a simple, cheap and reliable HPLC-MS method for use in TDM, in accordance with FDA and EMA guidelines. The optimized protein precipitation protocol required 50 μL of plasma, while chromatographic analysis could be performed in 12 min/sample. This method fulfilled the guidelines requirements and then, it was applied for routine DBV TDM in patients receiving off-label high doses (two 1500 + 1500 mg weekly infusions instead of 1000 + 500 mg), with normal renal function or undergoing hemodialysis: continuous hemodiafiltration caused a relevant reduction in DBV exposure, while intermittent dialysis showed comparable DBV concentrations with those of patients with normal renal function. This confirmed the eligibility of the presented method for use in TDM and its usefulness in clinical practice

Social Work and Countering Violent Extremism in Sweden and the UK

Social Work in Europe, is now being tasked with managing the “problems” of terrorism, i.e supporting those affected by terrorist attacks, managing returnees affiliated with Terrorist groups in the Middle East, or, as will be discussed here, identifying those at risk from radicalisation and extremism. Both Britain and Sweden have Counter-Terrorism policies, but recent developments in both countries, have made it a statutory requirement for social workers, to work within such policies. This paper seeks to explore the policies in both countries utilising a comparative approach, to consider the similarities in not only policy and practice, but also in the ethical consequences such policies pose for social workers across Europe. The exploration considers; the extent to which anti-radicalisation policies influence social work practices in Sweden and the UK and how they might undermine social work as a human rights profession. The results indicate that anti-radicalisation policies run the risk of reducing social work to become a ‘policing profession’ practicing social control. This has substantial consequences for social work and its global ethics, which should be considered and struggled against by social workers committed to principles of social justice and human rights

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign

Abstract: In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M ⊙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87’s spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

Protein kinase C epsilon is a key regulator of mitochondrial redox homeostasis in acute myeloid leukemia

Purpose: The intracellular redox environment of acute myeloid leukemia (AML) cells is often highly oxidized compared to healthy hematopoietic progenitors and this is purported to contribute to disease pathogenesis. However, the redox regulators that allow AML cell survival in this oxidized environment remain largely unknown. Experimental Design: Utilizing several chemical and genetically-encoded redox sensing probes across multiple human and mouse models of AML, we evaluated the role of the serine/ threonine kinase PKC-epsilon (PKCe) in intracellular redox biology, cell survival and disease progression. Results: We show that RNA interference-mediated inhibition of PKCe significantly reduces patient-derived AML cell survival as well as disease onset in a genetically engineered mouse model (GEMM) of AML driven by MLL-AF9. We also show that PKCe inhibition induces multiple reactive oxygen species (ROS) and that neutralization of mitochondrial ROS with chemical antioxidants or co-expression of the mitochondrial ROS-buffering enzymes SOD2 and CAT, mitigates the anti-leukemia effects of PKCe inhibition. Moreover, direct inhibition of SOD2 increases mitochondrial ROS and significantly impedes AML progression in vivo. Furthermore, we report that PKCe over-expression protects AML cells from otherwise-lethal doses of mitochondrial ROS-inducing agents. Proteomic analysis reveals that PKCe may control mitochondrial ROS by controlling the expression of regulatory proteins of redox homeostasis, electron transport chain flux, as well as outer mitochondrial membrane potential and transport. Conclusions: This study uncovers a previously unrecognized role for PKCe in supporting AML cell survival and disease progression by regulating mitochondrial ROS biology and positions mitochondrial redox regulators as potential therapeutic targets in AML