944 research outputs found

    Urate Handling in the Human Body

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    New developments in the forecasting of monthly overnight stays in the North Region of Portugal

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    The Tourism sector is of strategic importance to the North Region of Portugal and is growing. Forecasting monthly overnight stays in this region is, therefore, a relevant problem. In this paper, we analyze data more recent than those considered in previous studies and use them to develop and compare several forecasting models and methods. We conclude that the best results are achieved by models based on a non-parametric approach not considered so far for these data, the singular spectrum analysis.publishe

    Additive effects of two growth QTL on cattle chromosome 14

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    The document attached has been archived with permission from the World Congress on Genetics Applied to Livestock Production.DNA-marker technology has the potential to assist seed-stock beef producers with genetic improvement of traits that are difficult to measure, and to assist research workers in identifying chromosomal regions containing quantitative trait loci (QTL), and eventually genes, which control animal performance traits. A collaborative study was established in 1995 between AgResearch in New Zealand (NZ) and Adelaide University in Australia to search for DNA markers significantly linked to production, carcass and meat quality traits in beef cattle. The present paper reports on a sub-set of that data, namely evidence from microsatellite markers on chromosome (Chr) 14 of significant linkage to growth traits and hot carcass weight (HSCW) at a standard level of trim

    Lesinurad, a novel, oral compound for gout, acts to decrease serum uric acid through inhibition of urate transporters in the kidney.

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    BackgroundExcess body burden of uric acid promotes gout. Diminished renal clearance of uric acid causes hyperuricemia in most patients with gout, and the renal urate transporter (URAT)1 is important for regulation of serum uric acid (sUA) levels. The URAT1 inhibitors probenecid and benzbromarone are used as gout therapies; however, their use is limited by drug-drug interactions and off-target toxicity, respectively. Here, we define the mechanism of action of lesinurad (Zurampic®; RDEA594), a novel URAT1 inhibitor, recently approved in the USA and Europe for treatment of chronic gout.MethodssUA levels, fractional excretion of uric acid (FEUA), lesinurad plasma levels, and urinary excretion of lesinurad were measured in healthy volunteers treated with lesinurad. In addition, lesinurad, probenecid, and benzbromarone were compared in vitro for effects on urate transporters and the organic anion transporters (OAT)1 and OAT3, changes in mitochondrial membrane potential, and human peroxisome proliferator-activated receptor gamma (PPARγ) activity.ResultsAfter 6 hours, a single 200-mg dose of lesinurad elevated FEUA 3.6-fold (p < 0.001) and reduced sUA levels by 33 % (p < 0.001). At concentrations achieved in the clinic, lesinurad inhibited activity of URAT1 and OAT4 in vitro, did not inhibit GLUT9, and had no effect on ABCG2. Lesinurad also showed a low risk for mitochondrial toxicity and PPARγ induction compared to benzbromarone. Unlike probenecid, lesinurad did not inhibit OAT1 or OAT3 in the clinical setting.ConclusionThe pharmacodynamic effects and in vitro activity of lesinurad are consistent with inhibition of URAT1 and OAT4, major apical transporters for uric acid. Lesinurad also has a favorable selectivity and safety profile, consistent with an important role in sUA-lowering therapy for patients with gout

    A Case-control Study of Haemorrhagic Septicaemia in Buffaloes and Cattle in Karachi, Pakistan, in 2012

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    A retrospective epidemiological case–control study was performed in Karachi, Pakistan, from January to April 2013. The owners of 217 dairy cattle and buffalo farms from six different locations in Karachi were interviewed. The aim of the study was to identify risk factors associated with the presence of haemorrhagic septicaemia (HS). Farms with a history of at least one instance of sudden death in a dairy animal during 2012 and a positive clinical HS diagnosis (made by local veterinarians) were defined as cases. Farms having no history of sudden deaths in 2012 were defined as controls. Univariable analyses were initially conducted, and factors with P ≤ 0.25 were offered to a multivariable logistic regression model to identify putative risk factors. The final multivariable logistic model contained five factors. Vaccination was found to be a protective factor (OR = 0.22) along with the length of time cattle were kept on farm (months). For every extra month cattle were kept, the odds of HS disease were reduced by a factor of 0.9. In contrast, for every extra animal in a herd, the risk of infection increased by a factor of 1.01. Supplying underground water and the presence of foot and mouth disease on the farm increased the risk by 2.90 and 2.37, respectively. To understand the epidemiology of HS in Karachi dairy herds, more in-depth research is required to study the risk and protective factors identified in this survey and to evaluate risk mitigation strategies, where possible

    Paleogeodetic records of seismic and aseismic subduction from central Sumatran microatolls, Indonesia

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    We utilize coral microatolls in western Sumatra to document vertical deformation associated with subduction. Microatolls are very sensitive to fluctuations in sea level and thus act as natural tide gauges. They record not only the magnitude of vertical deformation associated with earthquakes (paleoseismic data), but also continuously track the long-term aseismic deformation that occurs during the intervals between earthquakes (paleogeodetic data). This paper focuses on the twentieth century paleogeodetic history of the equatorial region. Our coral paleogeodetic record of the 1935 event reveals a classical example of deformations produced by seismic rupture of a shallow subduction interface. The site closest to the trench rose 90 cm, whereas sites further east sank by as much as 35 cm. Our model reproduces these paleogeodetic data with a 2.3 m slip event on the interface 88 to 125 km from the trench axis. Our coral paleogeodetic data reveal slow submergence during the decades before and after the event in the areas of coseismic emergence. Likewise, interseismic emergence occurred before and after the 1935 event in areas of coseismic submergence. Among the interesting phenomenon we have discovered in the coral record is evidence of a large aseismic slip or “silent event” in 1962, 27 years after the 1935 event. Paleogeodetic deformation rates in the decades before, after, and between the 1935 and 1962 events have varied both temporally and spatially. During the 25 years following the 1935 event, submergence rates were dramatically greater than in prior decades. During the past four decades, however, rates have been lower than in the preceding decades, but are still higher than they were prior to 1935. These paleogeodetic records enable us to model the kinematics of the subduction interface throughout the twentieth century

    Gas hydrate on the northern Cascadia margin: regional geophysics and structural framework

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    Integrated Ocean Drilling Program Expedition 311 is based on extensive site survey data and historic research at the northern Cascadia margin since 1985. This research includes various regional geophysical surveys using a broad spectrum of seismic techniques, coring and logging by the Ocean Drilling Program Leg 146, heat flow measurements, shallow piston coring, and bottom video observations across a cold-vent field, as well as novel controlled-source electromagnetic and seafloor compliance surveying techniques. The wealth of data available allowed construction of structural cross-sections of the margin, development of models for the formation of gas hydrate in an accretionary prism, and estimation of gas hydrate and free gas concentrations. Expedition 311 established for the first time a transect of drill sites across the northern Cascadia margin to study the evolution of gas hydrate formation over the entire gas hydrate stability field of the accretionary complex. This paper reviews the tectonic framework at the northern Cascadia margin and summarizes the scientific studies that led to the drilling objectives of Expedition 311 Cascadia gas hydrate

    ICTV Virus Taxonomy Profile: Bornaviridae

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    Members of the family Bornaviridae produce enveloped virions containing a linear negative-sense non-segmented RNA genome of about 9 kb. Bornaviruses are found in mammals, birds, reptiles and fish. The most-studied viruses with public health and veterinary impact are Borna disease virus 1 and variegated squirrel bornavirus 1, both of which cause fatal encephalitis in humans. Several orthobornaviruses cause neurological and intestinal disorders in birds, mostly parrots. Endogenous bornavirus-like sequences occur in the genomes of various animals. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Bornaviridae, which is available at ictv.global/report/bornaviridae

    Forecasting Player Behavioral Data and Simulating in-Game Events

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    Understanding player behavior is fundamental in game data science. Video games evolve as players interact with the game, so being able to foresee player experience would help to ensure a successful game development. In particular, game developers need to evaluate beforehand the impact of in-game events. Simulation optimization of these events is crucial to increase player engagement and maximize monetization. We present an experimental analysis of several methods to forecast game-related variables, with two main aims: to obtain accurate predictions of in-app purchases and playtime in an operational production environment, and to perform simulations of in-game events in order to maximize sales and playtime. Our ultimate purpose is to take a step towards the data-driven development of games. The results suggest that, even though the performance of traditional approaches such as ARIMA is still better, the outcomes of state-of-the-art techniques like deep learning are promising. Deep learning comes up as a well-suited general model that could be used to forecast a variety of time series with different dynamic behaviors
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