Evaluation of a hand-held point-of-care analyser for measurement of creatinine in cats

ObjectivesThe aim of the study was to evaluate whether a handheld creatinine analyser (StatSensor Xpress; SSXp), available for human patients, can be used to measure creatinine reliably in cats.MethodsAnalytical performance was evaluated by determining within- and between-run coefficient of variation (CV, %), total error observed (TEobs, %) and sigma metrics. Fifty client-owned cats presenting for investigation of clinical disease had creatinine measured simultaneously, using SSXp (whole blood and plasma) and a reference instrument (Konelab, serum); 48 paired samples were included in the study. Creatinine correlation between methodologies (SSXp vs Konelab) and sample types (SSXpwhole bloodvs SSXpplasma) was assessed by Spearman’s correlation coefficient and agreement was determined using Bland–Altman difference plots. Each creatinine value was assigned an IRIS stage (1–4); correlation and agreement between Konelab and SSXp IRIS stages were evaluated.ResultsWithin-run CV (4.23–8.85%), between-run CV (8.95–11.72%), TEobs(22.15–34.92%) and sigma metrics (⩽3) did not meet desired analytical requirements. Correlation between sample types was high (SSXpwhole bloodvs SSXpplasma; r = 0.89), and between instruments was high (SSXpwhole bloodvs Konelabserum; r = 0.85) to very high (SSXpplasmavs Konelabserum; r = 0.91). Konelab and SSXpwhole bloodIRIS scores exhibited high correlation ( r = 0.76). Packed cell volume did not significantly affect SSXp determination of creatinine. Bland–Altman difference plots identified a positive bias for the SSXp (7.13 μmol/l SSXpwhole blood; 20.23 μmol/l SSXpplasma) compared with the Konelab. Outliers (1/48 whole blood; 2/48 plasma) occurred exclusively at very high creatinine concentrations. The SSXp failed to identify 2/21 azotaemic cats.Conclusions and relevanceAnalytical performance of the SSXp in feline patients is not considered acceptable. The SSXp exhibited a high to very high correlation compared with the reference methodology but the two instruments cannot be used interchangeably. Improvements in the SSXp analytical performance are needed before its use can be recommended in feline clinical practice.</jats:sec

Mars Surface Tunnel Element Concept

When the first human visitors on Mars prepare to return to Earth, they will have to comply with stringent planetary protection requirements. Apollo Program experience warns that opening an EVA hatch directly to the surface will bring dust into the ascent vehicle. To prevent inadvertent return of potential Martian contaminants to Earth, careful consideration must be given to the way in which crew ingress their Mars Ascent Vehicle (MAV). For architectures involving more than one surface element-such as an ascent vehicle and a pressurized rover or surface habitat-a retractable tunnel that eliminates extravehicular activity (EVA) ingress is an attractive solution. Beyond addressing the immediate MAV access issue, a reusable tunnel may be useful for other surface applications, such as rover to habitat transfer, once its primary mission is complete. A National Aeronautics and Space Administration (NASA) team is studying the optimal balance between surface tunnel functionality, mass, and stowed volume as part of the Evolvable Mars Campaign (EMC). The study team began by identifying the minimum set of functional requirements needed for the tunnel to perform its primary mission, as this would presumably be the simplest design, with the lowest mass and volume. This Minimum Functional Tunnel then becomes a baseline against which various tunnel design concepts and potential alternatives can be traded, and aids in assessing the mass penalty of increased functionality. Preliminary analysis indicates that the mass of a single-mission tunnel is about 237 kg, not including mass growth allowance

Platelet glycoprotein VI cluster size is related to thrombus formation and phosphatidylserine exposure in collagen-adherent platelets under arterial shear

Background: Collagen-induced platelet activation is predominantly mediated by glycoprotein (GP) VI through formation of receptor clusters that coincide with the accumulation of signaling molecules and are hypothesized to drive strong and sustained platelet activation. Objectives: To determine the importance of GPVI clusters for thrombus formation in whole blood under shear. Methods: We utilized whole blood microfluidics and an anti-GPVI nanobody (Nb), Nb28, labeled with AlexaFluor 488, to assess the distribution of GPVI on the surface of platelets adhering to a range of collagen-like substrates with different platelet activation potentials. Results: Automated analysis of GPVI surface distribution on platelets supported the hypothesis that there is a relationship between GPVI cluster formation, thrombus size, and phosphatidylserine (PS) exposure. Substrates that supported the formation of macroclusters also induced significantly bigger aggregates, with increased amounts of PS-exposing platelets in comparison to substrates where no GPVI clusters were detected. Furthermore, we demonstrate that only direct inhibition of GPVI binding, but not of downstream signaling, is able to disrupt cluster formation. Conclusion: Labeled anti-GPVI Nb28 permits visualization of GPVI clustering under flow conditions. Furthermore, whilst inhibition of downstream signaling does not affect clustering, it does prevent thrombus formation. Therefore, GPVI macroclustering is a prerequisite for thrombus formation and platelet activation, namely, PS exposure, on highly GPVI-dependent collagen surfaces

Inter-cultural differences in response to a computer-based anti-bullying intervention

Background and purpose: Many holistic anti-bullying interventions have been attempted, with mixed success, while little work has been done to promote a 'self-help' approach to victimisation. The rise of the ICT curriculum and computer support in schools now allows for approaches that benefit from technology to be implemented. This study evaluates the cross-cultural effects of a computer-based anti-bullying intervention on primary school-aged children's knowledge about bullying and relevant coping strategies. Programme description: FearNot! is an interactive computer-based virtual learning environment designed for use as an anti-bullying intervention. It includes interactive virtual agents who assume the most common participant roles found in episodes of bullying. FearNot! was used by children over three consecutive weeks to allow its effectiveness to be evaluated in a longitudinal in situ programme. Sample: Two comparable samples were drawn from the UK and Germany. In the UK, 651 participants (aged 8-11) were recruited from primary schools in Hertfordshire, Coventry and Warwickshire, whereas the 535 German participants (aged 7-10) were sourced from Grundschulen in the Bayern and Hessen regions. Because of lack of parental consent, late joiners and absences/missing responses, data from 908 participants (UK 493; Germany 415) were analysed. Design and methods: A quasi-experimental, pre/post-tests control group design employed pre-published and bespoke questionnaires to collect data. Descriptive and inferential analyses were conducted. Results: UK students possessed higher coping strategy knowledge scores than German participants, but German children's scores improved over time and as a result of the FearNot! intervention. Conclusions: Overall, while not effective at increasing children's coping strategy knowledge in this study, the FearNot! intervention could prove a useful classroom tool to approach the issue of bullying as part of a wider initiative. Cultural differences at baseline and reactions to the intervention are discussed

Low dose Btk inhibitors selectively block platelet activation by CLEC-2

Inhibitors of the tyrosine kinase Btk have been proposed as novel antiplatelet agents. In this study we show that low concentrations of the Btk inhibitor ibrutinib block CLEC-2-mediated activation and tyrosine phosphorylation including Syk and PLCγ2 in human platelets. Activation is also blocked in patients with X-linked agammaglobulinaemia (XLA) caused by a deficiency or absence of Btk. In contrast, the response to GPVI is delayed in the presence of low concentrations of ibrutinib or in patients with XLA, and tyrosine phosphorylation of Syk is preserved. A similar set of results is seen with the second-generation inhibitor, acalabrutinib. The differential effect of Btk inhibition in CLEC-2 relative to GPVI signalling is explained by the positive feedback role involving Btk itself, as well as ADP and thromboxane A2 mediated activation of P2Y12 and TP receptors, respectively. This feedback role is not seen in mouse platelets and, consistent with this, CLEC-2-mediated activation is blocked by high but not by low concentrations of ibrutinib. Nevertheless, thrombosis was absent in 8 out of 13 mice treated with ibrutinib. These results show that Btk inhibitors selectively block activation of human platelets by CLEC-2 relative to GPVI suggesting that they can be used at ‘low dose’ in patients to target CLEC-2 in thrombo-inflammatory disease

Experimental validation of computerised models of clustering of platelet glycoprotein receptors that signal via tandem SH2 domain proteins

The clustering of platelet glycoprotein receptors with cytosolic YxxL and YxxM motifs, including GPVI, CLEC-2 and PEAR1, triggers activation via phosphorylation of the conserved tyrosine residues and recruitment of the tandem SH2 (Src homology 2) domain effector proteins, Syk and PI 3-kinase. We have modelled the clustering of these receptors with monovalent, divalent and tetravalent soluble ligands and with transmembrane ligands based on the law of mass action using ordinary differential equations and agent-based modelling. The models were experimentally evaluated in platelets and transfected cell lines using monovalent and multivalent ligands, including novel nanobody-based divalent and tetravalent ligands, by fluorescence correlation spectroscopy. Ligand valency, receptor number, receptor dimerisation, receptor phosphorylation and a cytosolic tandem SH2 domain protein act in synergy to drive receptor clustering. Threshold concentrations of a CLEC-2-blocking antibody and Syk inhibitor act in synergy to block platelet aggregation. This offers a strategy for countering the effect of avidity of multivalent ligands and in limiting off-target effects

The X-ray source content of the XMM-Newton Galactic plane survey

We report the results of an optical campaign carried out by the XMM-Newton Survey Science Centre with the specific goal of identifying the brightest X-ray sources in the XMM-Newton Galactic plane survey. In addition to photometric and spectroscopic observations obtained at the ESO-VLT and ESO-3.6 m, we used cross-correlations with the 2XMMi, USNO-B1.0, MASS, and GLIMPSE catalogues to advance the identification process. Active coronae account for 16 of the 30 positively or tentatively identified X-ray sources and exhibit the softest X-ray spectra. Many of the identified hard X-ray sources are associated with massive stars, possible members of binary systems and emitting at intermediate X-ray luminosities of 1032−34 erg s−1. Among these are (i) a very absorbed, likely hyper-luminous star with X-ray/optical spectra and luminosities comparable to those of η Carina; (ii) a new X-rayselected WN8 Wolf-Rayet star in which most of the X-ray emission probably arises from wind collision in a binary; (iii) a new Be/X-ray star belonging to the growing class of γ-Cas analogues; and (iv) a possible supergiant X-ray binary of the kind discovered recently by INTEGRAL. One of the sources, XGPS-25, has a counterpart of moderate optical luminosity that exhibits HeII λ4686 and Bowen CIII-NIII emission lines, suggesting that this may be a quiescent or X-ray shielded low mass X-ray binary, although its X-ray properties might also be consistent with a rare kind of cataclysmic variable (CV). We also report the discovery of three new CVs, one of which is a likely magnetic system displaying strong X-ray variability. The soft (0.4–2.0 keV) band log N(>S )−log S curve is completely dominated by active stars in the flux range of 1 × 10−13 to 1 × 10−14 erg cm−2 s−1. Several active coronae are also detected above 2 keV suggesting that the population of RS CVn binaries contributes significantly to the hard X-ray source population. In total, we are able to identify a large fraction of the hard (2–10 keV) X-ray sources in the flux range of 1 × 10−12 to 1 × 10−13 erg cm−2 s−1 with Galactic objects at a rate consistent with what is expected for the Galactic contribution alone.We thank an anonymous referee for useful comments which helped to improve the quality of this paper. We are grateful to O. Herent for carrying out some of the observations presented in this work. This work has been supported in part by the DLR (Deutsches Zentrum für Luftund Raumfahrt) under grants 50 OX 0201 and 50 OX 0801. I.N. is supported by the Spanish Ministerio de Ciencia e Innovación under grants AYA2008-06166-C03-03 and CSD2006-70. This publication makes use of data products from the Two Micron All Sky Survey, which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technology, funded by the National Aeronautics and Space Administration and the National Science Foundation. The DENIS project has been partly funded by the SCIENCE and the HCM plans of the European Commission under grants CT920791 and CT940627. It is supported by INSU, MEN and CNRS in France, by the State of Baden-Württemberg in Germany, by DGICYT in Spain, by CNR in Italy, by FFwFBWF in Austria, by FAPESP in Brazil, by OTKA grants F-4239 and F-013990 in Hungary, and by the ESO C&EE grant A-04-046. Jean Claude Renault from IAP was the Project manager. Observations were carried out thanks to the contribution of numerous students and young scientists from all involved institutes, under the supervision of P. Fouqué, survey astronomer resident in Chile. The WHT is operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias. The observation presented here was taken as part of the ING service programme (proposal SW2005A06). This research has made use of Aladin, of the VizieR catalogue access tool and of Simbad at CDS, Strasbourg, France

Interspecies differences in protein expression do not impact the spatiotemporal regulation of glycoprotein VI mediated activation

Background Accurate protein quantification is a vital prerequisite for generating meaningful predictions when using systems biology approaches, a method that is increasingly being used to unravel the complexities of sub cellular interactions and as part of the drug discovery process. Quantitative proteomics, flow cytometry and western blotting have been extensively used to define human platelet protein copy numbers, yet for mouse platelets, a model widely used for platelet research, evidence is largely limited to a single proteomic dataset in which the total amount of proteins were generally comparatively higher than those found in human platelets. Objectives To investigate the functional implications of discrepancies between levels of mouse and human proteins in the GPVI signalling pathway using a systems pharmacology model of GPVI Methods The protein copy number of mouse platelet receptors was determined using flow cytometry. The Virtual Platelet, a mathematical model of Glycoprotein VI (GPVI) signalling, was used to determine the consequences of protein copy number differences observed between human and mouse platelets. Results and conclusion Despite the small size of mouse platelets compared to human platelets they possessed a greater density of surface receptors alongside a higher concentration of intracellular signalling proteins. Surprisingly the predicted temporal profile of Syk activity was similar in both species with predictions supported experimentally. Super resolution microscopy demonstrates that the spatial distribution of Syk is similar between species, suggesting that the spatial distribution of receptors and signalling molecules in activated platelets, rather than their copy number, is important for signalling pathway regulation

Comparing aerosol number and mass exhalation rates from children and adults during breathing, speaking and singing

Aerosol particles of respirable size are exhaled when individuals breathe, speak and sing and can transmit respiratory pathogens between infected and susceptible individuals. The COVID-19 pandemic has brought into focus the need to improve the quantification of the particle number and mass exhalation rates as one route to provide estimates of viral shedding and the potential risk of transmission of viruses. Most previous studies have reported the number and mass concentrations of aerosol particles in an exhaled plume. We provide a robust assessment of the absolute particle number and mass exhalation rates from measurements of minute ventilation using a non-invasive Vyntus Hans Rudolf mask kit with straps housing a rotating vane spirometer along with measurements of the exhaled particle number concentrations and size distributions. Specifically, we report comparisons of the number and mass exhalation rates for children (12–14 years old) and adults (19–72 years old) when breathing, speaking and singing, which indicate that child and adult cohorts generate similar amounts of aerosol when performing the same activity. Mass exhalation rates are typically 0.002–0.02 ng s(−1) from breathing, 0.07–0.2 ng s(−1) from speaking (at 70–80 dBA) and 0.1–0.7 ng s(−1) from singing (at 70–80 dBA). The aerosol exhalation rate increases with increasing sound volume for both children and adults when both speaking and singing