Prevalence of and risk factors for acute laminitis in horses treated with corticosteroids

A retrospective treated versus untreated study (study 1) and multicentre prospective cohort study (study 2) were undertaken to determine the prevalence of, and risk factors associated with, acute laminitis in horses treated with corticosteroids. All old treated with corticosteroids January–December 2014 (study 1) and January 2015–February 2017 (study 2) by two first opinion and referral hospitals in UK were included. Additionally, an untreated animal was identified for each treated animal (study one). Signalment, body condition (study 2 only), relevant medical history, primary condition, corticosteroid therapy prescribed and occurrence of acute laminitis during or within 14 days of cessation of corticosteroid treatment were recorded. For study 1, 205 cases and 205 controls were identified; two animals within each group (1 per cent) developed laminitis. In total, 1565 animals were included in study 2; laminitis period prevalence was 0.6 per cent (95 per cent CI 0.4 per cent to 1.2 per cent), with 10 cases in 1565 treated animals. There were significant associations between laminitis and breed (pony vs horse; p=0.01; univariable analysis only), the presence of a laminitis risk factor (history of laminitis or an underlying endocrinopathy; p<0.001; OR (95 per cent CI) 18.23 (5.05 to 65.87)) and body condition (overweight/obese vs not; p=0.04; OR (95 per cent CI) 4.0 (1.09 to 14.75))

The trypanosome alternative oxidase:a potential drug target?

New drugs against Trypanosoma brucei, the causative agent of Human African Trypanosomiasis, are urgently needed to replace the highly toxic and largely ineffective therapies currently used. The trypanosome alternative oxidase (TAO) is an essential and unique mitochondrial protein in these parasites and is absent from mammalian mitochondria, making it an attractive drug target. The structure and function of the protein are now well characterized, with several inhibitors reported in the literature which show potential as clinical drug candidates. In this review we provide an update on the functional activity and structural aspects of TAO. We then discuss TAO inhibitors reported to date, problems encountered with in vivo testing of these compounds, and discuss the future of TAO as a therapeutic target.PostprintPeer reviewe

Purinergic Signaling in Kidney Disease

Nucleotides are key subunits for nucleic acids and provide energy for intracellular metabolism. They can also be released from cells to act physiologically as extracellular messengers or pathologically as danger signals. Extracellular nucleotides stimulate membrane receptors in the P2 and P1 family. P2X are ATP- activated cation channels; P2Y and P1 are G-protein coupled receptors activated by ATP, ADP, UTP and UDP or adenosine, respectively. Renal P2 receptors influence both vascular contractility and tubular function. Renal cells also express ectonucleotidases that rapidly hydrolyze extracellular nucleoti des. These enzymes integrate this multi-receptor purinergic-signaling complex by determining the nucleotide milieu, as well as titrating receptor activation. Purinergic signaling also regulates immune cell function by modulating the synthesis and release of various cytokines such as IL1-β and IL-18 as part of inflammasome activation. Abnormal or excessive stimulation of this intricate paracrine system can be pro- or anti-inflammatory, and is also linked to necrosis and apoptosis. Kidney tissue injury causes a localized increase in ATP concentration, and sustained activation of P2 receptors can lead to renal glomerular, tubular and vascular cell damage. Purinergic receptors also regulate the activity and proliferation of fibroblasts, promoting both inflammation and fibrosis in chronic disease. In this short review we summarize some of the recent findings related to purinergic signaling in the kidney. We focus predominantly on the P2X7 receptor, discussing why antagonists have so far disappointed in clinical trials and how advances in our understanding of purinergic signaling might help to reposition these compounds as potential treatments for renal disease

The historical vanishing of the Blazhko effect of RR Lyr from GEOS and Kepler surveys

RR Lyr is one of the most studied variable stars. Its light curve has been regularly monitored since the discovery of the periodic variability in 1899. Analysis of all observed maxima allows us to identify two primary pulsation states defined as pulsation over a long (P0 longer than 0.56684 d) and a short (P0 shorter than 0.56682 d) primary pulsation period. These states alternate with intervals of 13-16 yr, and are well defined after 1943. The 40.8 d periodical modulations of the amplitude and the period (i.e. Blazhko effect) were noticed in 1916. We provide homogeneous determinations of the Blazhko period in the different primary pulsation states. The Blazhko period does not follow the variations of P0 and suddenly diminished from 40.8 d to around 39.0 d in 1975. The monitoring of these periodicities deserved and deserves a continuous and intensive observational effort. For this purpose we have built dedicated, transportable and autonomous small instruments, Very Tiny Telescopes (VTTs), to observe the times of maximum brightness of RR Lyr. As immediate results the VTTs recorded the last change of P0 state in mid-2009 and extended the time coverage of the Kepler observations, thus recording a maximum O-C amplitude of the Blazhko effect at the end of 2008, followed by the historically smallest O-C amplitude in late 2013. This decrease is still ongoing and VTT instruments are ready to monitor the expected increase in the next few years.Comment: 10 pages, 6 figures. Accepted for publication in MNRAS. Contents of appendix B may be requested to first autho

Towards A Census of Earth-mass Exo-planets with Gravitational Microlensing

Thirteen exo-planets have been discovered using the gravitational microlensing technique (out of which 7 have been published). These planets already demonstrate that super-Earths (with mass up to ~10 Earth masses) beyond the snow line are common and multiple planet systems are not rare. In this White Paper we introduce the basic concepts of the gravitational microlensing technique, summarise the current mode of discovery and outline future steps towards a complete census of planets including Earth-mass planets. In the near-term (over the next 5 years) we advocate a strategy of automated follow-up with existing and upgraded telescopes which will significantly increase the current planet detection efficiency. In the medium 5-10 year term, we envision an international network of wide-field 2m class telescopes to discover Earth-mass and free-floating exo-planets. In the long (10-15 year) term, we strongly advocate a space microlensing telescope which, when combined with Kepler, will provide a complete census of planets down to Earth mass at almost all separations. Such a survey could be undertaken as a science programme on Euclid, a dark energy probe with a wide-field imager which has been proposed to ESA's Cosmic Vision Programme.Comment: 10 pages. White Paper submission to the ESA Exo-Planet Roadmap Advisory Team. See also "Inferring statistics of planet populations by means of automated microlensing searches" by M. Dominik et al. (arXiv:0808.0004

Discovery of the optical counterpart and early optical observations of GRB990712

We present the discovery observations of the optical counterpart of the gamma-ray burster GRB990712 taken 4.16 hours after the outburst and discuss its light curve observed in the V, R and I bands during the first ~35 days after the outburst. The observed light curves were fitted with a power-law decay for the optical transient (OT), plus an additional component which was treated in two different ways. First, the additional component was assumed to be an underlying galaxy of constant brightness. The resulting slope of the decay is 0.97+/-0.05 and the magnitudes of the underlying galaxy are: V = 22.3 +/- 0.05, R = 21.75 +/- 0.05 and I = 21.35 +/- 0.05. Second, the additional component was assumed to be a galaxy plus an underlying supernova with a time-variable brightness identical to that of GRB980425, appropriately scaled to the redshift of GRB990712. The resulting slope of the decay is similar, but the goodness-of-fit is worse which would imply that either this GRB is not associated with an underlying supernova or the underlying supernova is much fainter than the supernova associated with GRB980425. The galaxy in this case is fainter: V = 22.7 +/- 0.05, R = 22.25 +/- 0.05 and I = 22.15 +/- 0.05; and the OT plus the underlying supernova at a given time is brighter. Measurements of the brightnesses of the OT and the galaxy by late-time HST observation and ground-based observations can thus assess the presence of an underlying supernova.Comment: To appear in Ap

Density estimates for Canada lynx vary among estimation methods

Abstract Unbiased population density estimates are critical for ecological research and wildlife management but are often difficult to obtain. Researchers use a variety of sampling and statistical methods to generate estimates of density, but few studies have compared estimates across methods. During 2016–2017, we surveyed Canada lynx (Lynx canadensis) in southwestern Yukon Territory, Canada, using track transect counts, hair snares, camera traps, live traps, and Global Positioning System (GPS) collars. From these data, we estimated lynx density with two linearly scaled count methods, one spatial mark–recapture method, three spatial mark–resight methods, and one cumulative‐time method. We found up to fivefold variation in point density estimates despite adhering to method requirements and assumptions in a manner consistent with other studies. Our results highlight the dependency of density estimates on sampling process and model assumptions and demonstrate the value of careful and unbiased sampling design. Further research is needed to fully assess the accuracy and limitations of the many wildlife density estimation methods that are currently in use so that techniques can be appropriately applied to typical study systems and species