Subjective and objective measures of adult bimodal users' listening

Inconsistencies exist between traditional objective measures such as speech recognition and localization, and subjective reports of bimodal benefit. The purpose of this study was to expand the set of objective measures of bimodal benefit to include non-traditional listening tests, and to examine possible correlations between objective measures of auditory perception and subjective satisfaction reports.

Predator Exclosures Enhance Reproductive Success but Increase Adult Mortality of Piping Plovers (Charadrius melodus)

Piping Plovers (Charadrius melodus) are listed as endangered throughout Canada and the United States Great Lakes region. Most attempts to increase their numbers have focused on enhancing reproductive success. Using 22 years of data collected by Parks Canada in Prince Edward Island National Park of Canada, we examined whether predator exclosures installed around Piping Plover nests increased nest success and hatching and fledging success when compared to nests without exclosures. Nests with exclosures were significantly more likely to hatch at least one egg than nests without exclosures, and they hatched a significantly greater number of young. The greater reproductive success observed in exclosed nests is likely due to the increased protection from predators that the exclosures conferred; significantly fewer exclosed nests were depredated than nonexclosed nests. However, significantly more exclosed than nonexclosed nests were abandoned by adults, and they had significantly greater adult mortality. Whether benefits of increased reproductive success from exclosures outweigh costs of increased abandonment and adult mortality remains unknown, but must be considered.

Cholinergic modulation of intrinsic fibre-evoked excitatory transmission contains a nicotinic component in immature but not adult rat piriform cortex, in vitro

The piriform cortex (PC) is highly prone to epileptogenesis, particularly in immature animals, where decreased muscarinic modulation of PC intrinsic fibre excitatory neurotransmission is implicated as a likely cause. However, whether higher levels of acetylcholine (ACh) release occur in immature vs. adult PC remains unclear. We investigated this using in vitro extracellular electrophysiological recording techniques. Intrinsic fibre-evoked extracellular field potentials (EFPs) were recorded from layers II to III in PC brain slices prepared from immature (P14-18) and adult (P>40) rats. Adult and immature PC EFPs were suppressed by eserine (1muM) or neostigmine (1muM) application, with a greater suppression in immature ( approximately 40%) than adult ( approximately 30%) slices. Subsequent application of atropine (1muM) reversed EFP suppression, producing supranormal ( approximately 12%) recovery in adult slices, suggesting that suppression was solely muscarinic ACh receptor-mediated and that some 'basal' cholinergic 'tone' was present. Conversely, atropine only partially reversed anticholinesterase effects in immature slices, suggesting the presence of additional non-muscarinic modulation. Accordingly, nicotine (50muM) caused immature field suppression ( approximately 30%) that was further enhanced by neostigmine, whereas it had no effect on adult EFPs. Unlike atropine, nicotinic antagonists, mecamylamine and methyllycaconitine, induced immature supranormal field recovery ( approximately 20%) following anticholinesterase-induced suppression (with no effect on adult slices), confirming that basal cholinergic 'tone' was also present. We suggest that nicotinic inhibitory cholinergic modulation occurs in the immature rat PC intrinsic excitatory fibre system, possibly to complement the existing, weak muscarinic modulation, and could be another important developmentally regulated system governing immature PC susceptibility towards epileptogenesis.

Errors associated with preparation of adult and paediatric parenteral nutrition in UK hospital pharmacies

Rationale: In UK hospitals, the preparation of all total parenteral nutrition (TPN) products must be made in the pharmacy as TPNs are categorised as high-risk injectables (NPSA/2007/20). The National Aseptic Error Reporting Scheme has been collecting data on pharmacy compounding errors in the UK since August 2003. This study reports on types of error associated with the preparation of TPNs, including the stage at which these were identified and potential and actual patient outcomes. Methods: Reports of compounding errors for the period 1/2004 - 3/2007 were analysed on an Excel spreadsheet. Results: Of a total of 3691 compounding error reports, 674 (18%) related to TPN products; 548 adult vs. 126 paediatric. A significantly higher proportion of adult TPNs (28% vs. 13% paediatric) were associated with labelling errors and a significantly higher proportion of paediatric TPNs (25% vs. 15% adult) were associated with incorrect transcriptions (Chi-Square Test; p<0.005). Labelling errors were identified equally by pharmacists (42%) and technicians (48%) with technicians detecting mainly at first check and pharmacists at final check. Transcription errors were identified mainly by technicians (65% vs. 27% pharmacist) at first check. Incorrect drug selection (13%) and calculation errors (9%) were associated with adult and paediatric TPN preparations in the same ratio. One paediatric TPN error detected at first check was considered potentially catastrophic; 31 (5%) errors were considered of major and 38 (6%) of moderate potential consequence. Five errors (2 moderate, 1 minor) were identified during or after administration. Conclusions: While recent UK patient safety initiatives are aimed at improving the safety of injectable medicines in clinical areas, the current study highlights safety problems that exist within pharmacy production units. This could be used in the creation of an error management tool for TPN compounding processes within hospital pharmacies.

Δ9-tetrahydrocannabivarin suppresses in vitro epileptiform and in vivo seizure activity in adult rat

Purpose: We assessed the anticonvulsant potential of the phytocannabinoid Δ9-tetrahydrocannabivarin (Δ9-THCV) by investigating its effects in an in vitro piriform cortex (PC) brain slice model of epileptiform activity, on cannabinoid CB1 receptor radioligand-binding assays and in a generalized seizure model in rats. Methods: Δ9-THCV was applied before (10 μmΔ9-THCV) or during (10–50 μmΔ9-THCV) epileptiform activity induced by Mg2+-free extracellular media in adult rat PC slices and measured using multielectrode array (MEA) extracellular electrophysiologic techniques. The actions of Δ9-THCV on CB1 receptors were examined using [3H]SR141716A competition binding and [35S]GTPS assays in rat cortical membranes. Effects of Δ9-THCV (0.025–2.5 mg/kg) on pentylenetetrazole (PTZ)–induced seizures in adult rats were also assessed. Results: After induction of stable spontaneous epileptiform activity, acute Δ9-THCV application (≥20 μm) significantly reduced burst complex incidence and the amplitude and frequency of paroxysmal depolarizing shifts (PDSs). Furthermore, slices pretreated with 10 μmΔ9-THCV prior to induction of epileptiform activity exhibited significantly reduced burst complex incidence and PDS peak amplitude. In radioligand-binding experiments, Δ9-THCV acted as a CB1 receptor ligand, displacing 0.5 nm [3H]SR141716A with a Ki∼290 nm, but exerted no agonist stimulation of [35S]GTPS binding. In PTZ-induced seizures in vivo, 0.25 mg/kg Δ9-THCV significantly reduced seizure incidence. Discussion: These data demonstrate that Δ9-THCV exerts antiepileptiform and anticonvulsant properties, actions that are consistent with a CB1 receptor–mediated mechanism and suggest possible therapeutic application in the treatment of pathophysiologic hyperexcitability states.

An evaluation of Bayesian designs for dose-escalation studies in healthy volunteers

In this paper, Bayesian decision procedures previously proposed for dose-escalation studies in healthy volunteers are reviewed and evaluated. Modifications are made to the expression of the prior distribution in order to make the procedure simpler to implement and a more relevant criterion for optimality is introduced. The results of an extensive simulation exercise to establish the proper-ties of the procedure and to aid choice between designs are summarized, and the way in which readers can use simulation to choose a design for their own trials is described. The influence of the value of the within-subject correlation on the procedure is investigated and the use of a simple prior to reflect uncertainty about the correlation is explored. Copyright (c) 2005 John Wiley & Sons, Ltd.

Molecular, cellular and physiological investigation of myostatin propeptide-mediated muscle growth in adult mice

Inhibition of myostatin signalling or its biological activity has recently emerged as a potential remedial approach against muscle wasting and degenerative diseases such as muscular dystrophies. In the present study we systemically administered a recombinant AAV8 vector expressing a mutated myostatin propeptide (AAV8ProMyo) to healthy mice in order to assess its impact on the histological, cellular and physiological properties of the skeletal muscle, exploiting the fact that myostatin is naturally inhibited by its own propeptide. We report that a single intravenous administration of AAV8ProMyo leads to increases in muscle mass of tibialis anterior, extensor digitorum longus and gastrocnemius muscles 8 weeks post-injection and tibialis anterior, gastrocnemius and rectus femoris muscles 17 weeks post-injection. Moreover, treatment resulted in muscle fibre hypertrophy but not hyperplasia, with IIB myofibres responding to the greatest extent following propeptide-induced myostatin inhibition. Additionally, myofibre nuclear: cytoplasmic ratio was decreased in the AAV8ProMyo treated animals. Importantly, the hypertrophic EDL muscle 8 weeks after AAV8ProMyo treatment did not show the dramatic decrease in specific force displayed by the germline myostatin null mice. (C) 2009 Elsevier B.V. All rights reserved.

Implementation of a Bayesian design in a dose-escalation study of an experimental agent in healthy volunteers

Bayesian decision procedures have recently been developed for dose escalation in phase I clinical trials concerning pharmacokinetic responses observed in healthy volunteers. This article describes how that general methodology was extended and evaluated for implementation in a specific phase I trial of a novel compound. At the time of writing, the study is ongoing, and it will be some time before the sponsor will wish to put the results into the public domain. This article is an account of how the study was designed in a way that should prove to be safe, accurate, and efficient whatever the true nature of the compound. The study involves the observation of two pharmacokinetic endpoints relating to the plasma concentration of the compound itself and of a metabolite as well as a safety endpoint relating to the occurrence of adverse events. Construction of the design and its evaluation via simulation are presented.

Forced expression of the cyclin B1-CDC2 complex induces proliferation in adult rat cardiomyocytes

Repair of the mature mammalian myocardium following injury is impaired by the inability of the majority of cardiomyocytes to undergo cell division. We show that overexpression of the cyclin B1-CDC2 (cell division cycle 2 kinase) complex re-initiates cell division in adult cardiomyocytes. Thus strategies targeting the cyclin B1-CDC2 complex might re-initiate cell division in mature cardiomyocytes in vivo and facilitate myocardial regeneration following injury.

Dynamics and foraging behaviour of adult hornet robberflies, Asilus crabroniformis: implications for conservation strategy

Mark resighting studies of the hornet robberfly, Asilus crabroniformis, were carried out during the flight seasons of 1999 and 2000 on agricultural land on the Chilterns in Oxfordshire, UK. Six patches of land were identified which contained characteristics thought to be attractive to hornet robberflies. One hundred and twenty eight adults were marked in 1999 and 257 in 2000. Marking was carried out on one of the patches, but resighting observations were collected from all six sites. The daily population sizes were estimated using the Jolly-Seber method. The daily population size peaked between 50 and 72 from 23 August until 13 September in 2000. This was very similar to the peak population size of between 50 and 74 estimated for 1999. Adults were found to be capable of living for nearly 5 weeks. The maximum linear distance from the point of marking that any individual moved across the study site was 625 m, but some individuals moved over 400 m in a single day. Unsuitable habitat (suburban gardens and a main road) did not present a barrier to dispersal. Males were more likely than females to loiter in sites peripheral to the breeding site, whilst females seemed to be more tied to the breeding site. Most adults were caught from dung piles, but insects avoided fresh dung and preferred instead dung that was well into the process of drying out. A variety of insect species were taken as prey, including many beetles and flies. The findings of the study are discussed in relation to the management of the landscape to enhance the long-term prospects of the hornet robberfly in the UK, and to achieve the UK Biodiversity Action Plan target for this species.