1,407 research outputs found

    Evaluation of the incremental cost to the National Health Service of prescribing analogue insulin

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    Introduction Insulin analogues have become increasingly popular despite their greater cost compared with human insulin. The aim of this study was to calculate the incremental cost to the National Health Service (NHS) of prescribing analogue insulin preparations instead of their human insulin alternatives. Methods Open-source data from the four UK prescription pricing agencies from 2000 to 2009 were analysed. Cost was adjusted for inflation and reported in UK pounds at 2010 prices. Results Over the 10-year period, the NHS spent a total of £2732 million on insulin. The total annual cost increased from £156 million to £359 million, an increase of 130%. The annual cost of analogue insulin increased from £18.2 million (12% of total insulin cost) to £305 million (85% of total insulin cost), whereas the cost of human insulin decreased from £131 million (84% of total insulin cost) to £51 million (14% of total insulin cost). If it is assumed that all patients using insulin analogues could have received human insulin instead, the overall incremental cost of analogue insulin was £625 million. Conclusion Given the high marginal cost of analogue insulin, adherence to prescribing guidelines recommending the preferential use of human insulin would have resulted in considerable financial savings over the period

    Survival of Radio-Marked Versus Leg-Banded Northern Bobwhite in Kentucky

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    Understanding the impact of radiomarking northern bobwhite (Colinus virginianus) survival is essential because of the widespread reliance on radiotelemetry to assess vital population parameters. We conducted an assessment of bobwhite populations within the Central Hardwoods Bird Conservation Region using leg banding and radiotelemetry on Peabody Wildlife Management Area, a 3,330-ha reclaimed surface mine in western Kentucky. We captured bobwhites using baited funnel traps during a 112-day period (23 Jul-11 Nov 2010) and marked 180 with necklace-style radio-transmitters (6 g) and 256 birds with only leg bands. Eighty-five birds were opportunistically recaptured in funnel traps, of which 81 were used in developing survival estimates. We used the Cormack-Jolly-Seber model in Program MARK to estimate periodic survival rates (PSR) of both sample groups. Candidate models which included body mass as a covariate explained the most variability in survival. The estimated PSR was 0.309 6 0.109 based on the best approximating model and was 0.302 6 0.108 from model averaging. We calculated a point of inflection for this model, which suggested a mass ‘threshold’ of 131g, above which survival improved at a decreasing rate. The model including only the radio-transmitter effect had a DAICc .3 and was considered to be non-plausible. Further research with larger samples is needed to develop more robust survival models to fully assess the effects of radiomarking bobwhites. It does not appear, based on our study, that radio transmitters adversely affect survival of northern bobwhite

    Northern Bobwhite Survival Related to Movement on a Reclaimed Surface Coal Mine

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    Reclaimed coal mines represent opportunity to provide large tracts of early succession habitat essential to northern bobwhite (Colinus virginianus) populations. However, little research has been conducted to explore the potential of reclaimed mine sites and examine bobwhite ecology on these unique areas. Reclaimed mines in Kentucky were planted to non-native species, such as sericea lespedeza (Lespedeza cuneata) and tall fescue (Festuca arundinacea), which do not provide suitable structure for northern bobwhite brood-rearing and movement. Fallow disking (in blocks and linear firebreaks) and planting food plots are part of current management efforts to improve food availability and habitat structure for broods. We trapped and radiomarked 266 northern bobwhites between April 2010 and September 2011 on Peabody Wildlife Management Area, a 3,330-ha reclaimed coal mine in western Kentucky, USA to investigate the effects of current management practices on movement and survival. We calculated seasonal daily movement as the Euclidean distance from a location on day 1 to day 2. Breeding season (1 Apr-30 Sep) movement averaged 128 m in 2010 and 147 m in 2011. Daily movement averaged 163 m during the 2010–2011 non-breeding (1 Oct-31 Mar) season. Multiple regression analysis indicated annual food plots, disk blocks, firebreaks, and roads did not explain variation within daily movement regardless of season (R2 0.04). Individual bird/covey, precipitation, hours between locations, and average temperature also poorly explained movement variation. We used Program MARK to model the effect of season, year, mean daily movement, mean distance to annual food plots, disk blocks, firebreaks, and roads on survival. The season (breeding/non-breeding) model explained 81% of the variation in survival, and the year model explained 13%, suggesting management was not driving survival. We do not believe disking should be discontinued, although it did not influence movement, as it can improve vegetation structure important to nest-site selection and broods

    Phosphomimetic Mutation of Ser-187 of SNAP-25 Increases both Syntaxin Binding and Highly Ca2+-sensitive Exocytosis

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    The phosphorylation targets that mediate the enhancement of exocytosis by PKC are unknown. PKC phosporylates the SNARE protein SNAP-25 at Ser-187. We expressed mutants of SNAP-25 using the Semliki Forest Virus system in bovine adrenal chromaffin cells and then directly measured the Ca2+ dependence of exocytosis using photorelease of caged Ca2+ together with patch-clamp capacitance measurements. A flash of UV light used to elevate [Ca2+]i to several μM and release the highly Ca2+-sensitive pool (HCSP) of vesicles was followed by a train of depolarizing pulses to elicit exocytosis from the less Ca2+-sensitive readily releasable pool (RRP) of vesicles. Carbon fiber amperometry confirmed that the amount and kinetics of catecholamine release from individual granules were similar for the two phases of exocytosis. Mimicking PKC phosphorylation with expression of the S187E SNAP-25 mutant resulted in an approximately threefold increase in the HCSP, whereas the response to depolarization increased only 1.5-fold. The phosphomimetic S187D mutation resulted in an ∼1.5-fold increase in the HCSP but a 30% smaller response to depolarization. In vitro binding assays with recombinant SNARE proteins were performed to examine shifts in protein–protein binding that may promote the highly Ca2+-sensitive state. The S187E mutant exhibited increased binding to syntaxin but decreased Ca2+-independent binding to synaptotagmin I. Mimicking phosphorylation of the putative PKA phosphorylation site of SNAP-25 with the T138E mutation decreased binding to both syntaxin and synaptotagmin I in vitro. Expressing the T138E/ S187E double mutant in chromaffin cells demonstrated that enhancing the size of the HCSP correlates with an increase in SNAP-25 binding to syntaxin in vitro, but not with Ca2+-independent binding of SNAP-25 to synaptotagmin I. Our results support the hypothesis that exocytosis triggered by lower Ca2+ concentrations (from the HCSP) occurs by different molecular mechanisms than exocytosis triggered by higher Ca2+ levels

    Monitoring Northern Bobwhite Breeding Populations in the Central Hardwoods Bird Conservation Region

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    Monitoring northern bobwhite (Colinus virginianus) breeding populations is an important component of the National Bobwhite Conservation Initiative as a means of evaluating success of achieving population goals. Northern bobwhite populations declined by 3.8% from 1980 to 2006 in the Central Hardwoods Bird Conservation Region (CHBCR). Northern bobwhite research in the CHBCR is limited and population trend estimates are based on North American Breeding Bird Survey (BBS) data. Monitoring northern bobwhite populations and developing accurate population estimates by incorporating detection functions and occupancy estimates are important components of the conservation initiative in this region. We documented northern bobwhite abundance throughout the CHBCR via a roadside-based removal and distance sampling survey method, and assessed differences in detection with respect to observer, northern bobwhite relative abundance, and land cover. We also addressed the potential for a roadside survey bias to ascertain if there was a seasonal, or site effect on northern bobwhite detection and occupancy through repeated surveys. Finally, we measured northern bobwhite calling rates by time of day and day of the breeding season to assess bobwhite availability for detection with radiotelemetry data. The spatially-balanced, roadside, monitoring strategy used counties as basic sampling units within bobwhite focal areas in the CHBCR (n 1⁄4 37 counties). We randomly located 5, 15-km monitoring routes in each focal county along secondary roads. We conducted 5-min unlimited distance point counts along each route (30 counts/route) from May through July, 2008–2011. We conducted off-road and radiotelemetry surveys on Peabody Wildlife Management Area (PWMA), and additional off-road surveys on Fort Campbell Military Base, Tennessee-Kentucky and on private lands in Livingston County, Kentucky from May through July, 2010–2011.We detected 6,440 individual northern bobwhite on roadside survey routes; .95% of the survey routes had at least 1 northern bobwhite detection. We developed a suite of 17 a priori removal models in Program MARK to estimate roadside survey detection probabilities. The best model included differences in time interval detection, observer, and 3 covariates: distance from the observer, number of individuals aurally detected, and percent forested habitat within a 100-m radius of the point count. Detection probabilities were greatest during the first minute of detection, and then decreased. Detection probabilities (6 SD) decreased as distance from the observer (b 1⁄4 0.0020 6 0.0005, n 1⁄4 6,440) increased, but increased as the number of individuals detected at a point (b 1⁄4 0.15 6 0.04, n 1⁄4 6,440) increased. We used the most parsimonious model and mean covariate values to generate overall parameter estimates, which differed between observers and time intervals. We detected 637 individual northern bobwhite on 90 off-road transects across 4 sites from 2010 to 2011. We developed a suite of 10 a priori occupancy models in Program MARK to estimate off-road survey detection probabilities and site occupancy. Detection probabilities were greater (.26%) during the second point count visit (q 1⁄4 0.69 6 0.03) versus first (q 1⁄4 0.51 6 0.04) and third (q 1⁄4 0.47 6 0.04) visits (n 1⁄4 270). Detection probability increased as relative abundance increased (b 1⁄4 2.90 6 0.22, n 1⁄4 270). Occupancy was held constant and was not affected by any covariates evaluated. Peak northern bobwhite detection probabilities occurred from 1 to 25 June, an important consideration for population models that use breeding season survey data. Distance from road was not a significant grouping variable in any of the models, suggesting that roadside bias may not be an important consideration in designing bobwhite monitoring strategies. We located 295 radio-marked male bobwhites from 2010 to 2011. Marked males called on 115 of 295 points (39.0%). The furthest distance a radio-marked male moved during the survey period was 60 m, and movement distances were generally small (x ̄ 1⁄4 4.2 6 10.3 m, n 1⁄4 295). We compared 8 a priori time-of-detection models in Program MARK to estimate radiotelemetry survey detection probabilities. We grouped surveys based on year and included time-of-day, and day- of-year as additional temporal covariates. Detection probability was inversely related to time of day (b 1⁄4 0.04 6 0.10, n 1⁄4 105), but positively related to day of year (b 1⁄4 0.010 6 0.008, n 1⁄4 105); b estimates overlapped 0 suggested weak relationships. Our results documented the first attempt to explicitly model differences in northern bobwhite detection related to spatial (potential roadside biases, habitat parameters, northern bobwhite distances), temporal (seasonality, annual fluctuations), and behavioral (observer, northern bobwhite relative abundance) variables. We used a combination of 3 methodologies to estimate detection parameters and will adjust indices of relative abundance and density estimates across a broad spatial extent. Our spatially-balanced roadside survey can be effectively used to monitor northern bobwhite populations across broad spatial extents and incorporates the components of detection to improve estimates of northern bobwhite relative abundance

    Evaluation of elicitation methods to quantify Bayes linear models

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    The Bayes linear methodology allows decision makers to express their subjective beliefs and adjust these beliefs as observations are made. It is similar in spirit to probabilistic Bayesian approaches, but differs as it uses expectation as its primitive. While substantial work has been carried out in Bayes linear analysis, both in terms of theory development and application, there is little published material on the elicitation of structured expert judgement to quantify models. This paper investigates different methods that could be used by analysts when creating an elicitation process. The theoretical underpinnings of the elicitation methods developed are explored and an evaluation of their use is presented. This work was motivated by, and is a precursor to, an industrial application of Bayes linear modelling of the reliability of defence systems. An illustrative example demonstrates how the methods can be used in practice

    Observations of SN 2017ein Reveal Shock Breakout Emission and A Massive Progenitor Star for a Type Ic Supernova

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    We present optical and ultraviolet observations of nearby type Ic supernova SN 2017ein as well as detailed analysis of its progenitor properties from both the early-time observations and the prediscovery Hubble Space Telescope (HST) images. The optical light curves started from within one day to \sim275 days after explosion, and optical spectra range from \sim2 days to \sim90 days after explosion. Compared to other normal SNe Ic like SN 2007gr and SN 2013ge, \mbox{SN 2017ein} seems to have more prominent C{\footnotesize II} absorption and higher expansion velocities in early phases, suggestive of relatively lower ejecta mass. The earliest photometry obtained for \mbox{SN 2017ein} show indications of shock cooling. The best-fit obtained by including a shock cooling component gives an estimate of the envelope mass as \sim0.02 M_{\odot} and stellar radius as 8±\pm4 R_{\odot}. Examining the pre-explosion images taken with the HST WFPC2, we find that the SN position coincides with a luminous and blue point-like source, with an extinction-corrected absolute magnitude of MV_V\sim-8.2 mag and MI_I\sim-7.7 mag.Comparisons of the observations to the theoretical models indicate that the counterpart source was either a single WR star or a binary with whose members had high initial masses, or a young compact star cluster. To further distinguish between different scenarios requires revisiting the site of the progenitor with HST after the SN fades away.Comment: 28 pages, 19 figures; accepted for publication in The Astrophysical Journa

    Compulsory admission at first presentation to services for psychosis: does ethnicity still matter? Findings from two population-based studies of first episode psychosis

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    Objectives Compared with the majority population, those from minority ethnic groups in the UK are more likely to be admitted compulsorily during a first episode of psychosis (FEP). We investigated whether these disparities in pathways in to care continue. Methods We analysed data from two first episode psychosis studies, conducted in the same geographical area in south London 15 years apart: the Aetiology and Ethnicity in Schizophrenia and Other Psychosis (AESOP) and the Clinical Record Interactive Search-First Episode Psychosis (CRIS-FEP) studies. The inclusion/exclusion criteria for case ascertainment for first episode psychosis were identical across the two studies. We performed multivariable logistic regression to estimate odds of compulsory admission by ethnic group, controlling for confounders. Participants Two hundred sixty-six patients with first episode psychosis, aged 18–64 years, who presented to mental health services in south London in 1997–1999 and 446 with FEP who presented in 2010–2012. Results When the two samples were compared, ethnic differences in compulsory admission appear to have remained the same for black African patients, i.e. three times higher than white British in both samples: AESOP (adj. OR = 3.96; 95% CI = 1.80–8.71) vs. CRIS-FEP (adj. OR = 3.12; 95% CI = 1.52–6.35). Black Caribbean patients were three times more likely to be compulsorily admitted in AESOP (adj. OR = 3.20; 95% CI = 1.56–6.54). This was lower in the CRIS-FEP sample (adj. OR = 1.68; 95% CI = 0.71–3.98) and did not meet conventional levels for statistical significance. Conclusion Ethnicity is strongly associated with compulsory admissions at first presentation for psychosis with evidence of heterogeneity across groups, which deserves further research
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