Beaufort trout MicroPlex:A high-throughput multiplex platform comprising 38 informative microsatellite loci for use in resident and anadromous (sea trout) brown trout Salmo trutta genetic studies

A flexible panel consisting of 38 informative microsatellite markers for Salmo trutta is described. These markers were selected from a pool of over 150 candidate loci that can be readily amplified in four multiplex PCR groups but other permutations are also possible. The basic properties of each markers were assessed in six population samples from both the Burrishoole catchment, in the west of Ireland, and Lough Neagh, in Northern Ireland. A method to assess the relative utility of individual markers for the detection of population genetic structuring is also described. Given its flexibility, technical reliability and high degree of informativeness, the use of this panel of markers is advocated as a standard for S. trutta genetic studies. © 2013 The Authors. Journal of Fish Biology © 2013 The Fisheries Society of the British Isles.

High-throughput single-nucleotide polymorphism-based typing of shared Pseudomonas aeruginosa strains in cystic fibrosis patients using the Sequenom iPLEX platform

Shared strains of Pseudomonas aeruginosa are now well recognized in people with cystic fibrosis (CF), and suitable P. aeruginosa laboratory typing tools are pivotal to understanding their clinical significance and guiding infection control policies in CF clinics. We therefore compared a single-nucleotide polymorphism (SNP)-based typing method using Sequenom iPLEX matrix-assisted laser desorption ionization with time-of-flight mass spectrometry (MALDI-TOF MS) with typing methods used routinely by our laboratory. We analysed 617 P. aeruginosa isolates that included 561 isolates from CF patients collected between 2001 and 2009 in two Brisbane CF clinics and typed previously by enterobacterial repetitive intergenic consensus (ERIC)-PCR, as well as 56 isolates from non-CF patients analysed previously by multilocus sequence typing (MLST). The isolates were tested using a P. aeruginosa Sequenom iPLEX MALDI-TOF (PA iPLEX) method comprising two multiplex reactions, a 13-plex and an 8-plex, to characterize 20 SNPs from the P. aeruginosa housekeeping genes acsA, aroE, guaA, mutL, nuoD, ppsA and trpE. These 20 SNPs were employed previously in a real-time format involving 20 separate assays in our laboratory. The SNP analysis revealed 121 different SNP profiles for the 561 CF isolates. Overall, there was at least 96% agreement between the ERIC-PCR and SNP analyses for all predominant shared strains among patients attending our CF clinics: AUST-01, AUST-02 and AUST-06. For the less frequently encountered shared strain AUST-07, 6/25 (24%) ERIC-PCR profiles were misidentified initially as AUST-02 or as unique, illustrating the difficulty of gel-based analyses. SNP results for the 56 non-CF isolates were consistent with previous MLST data. Thus, the PA iPLEX format provides an attractive high-throughput alternative to ERIC-PCR for large-scale investigations of shared P. aeruginosa strains.

Price Discovery in the Dual-Platform US Treasury Market

Inter-dealer trading in US Treasury securities is almost equally divided between two electronic trading platforms that have only slight differences in terms of their relative liquidity and transparency. BrokerTec is more active in the trading of 2-, 5-, and 10-year T-notes while eSpeed has more active trading in the 30-year bond. Over the period studied, eSpeed provides a more pre-trade transparent platform than BrokerTec. We examine the contribution to ‘price discovery’ of activity in the two platforms using high frequency data. We find that price discovery does not derive equally from the two platforms and that the shares vary across term to maturity. This can be traced to differential trading activities and transparency of the two platforms.

A Coordination and Ligand Replacement Based Three-Input Colorimetric Logic Gate Sensing Platform for Melamine, Mercury Ions, and Cysteine

Discrimination of different species in various target scopes within a single sensing platform can provide many advantages such as simplicity, rapidness, and cost effectiveness. Here we design a three-input colorimetric logic gate based on the aggregation and anti-aggregation of gold nanoparticles (Au NPs) for the sensing of melamine, cysteine, and Hg2+. The concept takes advantages of the highly specific coordination and ligand replacement reactions between melamine, cysteine, Hg2+, and Au NPs. Different outputs are obtained with the combinational inputs in the logic gates, which can serve as a reference to discriminate different analytes within a single sensing platform. Furthermore, besides the intrinsic sensitivity and selectivity of Au NPs to melamine-like compounds, the “INH” gates of melamine/cysteine and melamine/Hg2+ in this logic system can be employed for sensitive and selective detections of cysteine and Hg2+, respectively.

Making randomised trials more efficient: report of the first meeting to discuss the Trial Forge platform

Randomised trials are at the heart of evidence-based healthcare, but the methods and infrastructure for conducting these sometimes complex studies are largely evidence free. Trial Forge (www.trialforge.org) is an initiative that aims to increase the evidence base for trial decision making and, in doing so, to improve trial efficiency.

This paper summarises a one-day workshop held in Edinburgh on 10 July 2014 to discuss Trial Forge and how to advance this initiative. We first outline the problem of inefficiency in randomised trials and go on to describe Trial Forge. We present participants' views on the processes in the life of a randomised trial that should be covered by Trial Forge.

General support existed at the workshop for the Trial Forge approach to increase the evidence base for making randomised trial decisions and for improving trial efficiency. Agreed upon key processes included choosing the right research question; logistical planning for delivery, training of staff, recruitment, and retention; data management and dissemination; and close down. The process of linking to existing initiatives where possible was considered crucial. Trial Forge will not be a guideline or a checklist but a 'go to' website for research on randomised trials methods, with a linked programme of applied methodology research, coupled to an effective evidence-dissemination process. Moreover, it will support an informal network of interested trialists who meet virtually (online) and occasionally in person to build capacity and knowledge in the design and conduct of efficient randomised trials.

Some of the resources invested in randomised trials are wasted because of limited evidence upon which to base many aspects of design, conduct, analysis, and reporting of clinical trials. Trial Forge will help to address this lack of evidence.

Design of a Dissolving Microneedle Platform for Transdermal Delivery of a Fixed-Dose Combination of Cardiovascular Drugs

Microneedles (MNs) are a minimally invasive drug delivery platform, designed to enhance transdermal drug delivery by breaching the stratum corneum. For the first time, this study describes the simultaneous delivery of a combination of three drugs using a dissolving polymeric MN system. In the present study, aspirin, lisinopril dihydrate, and atorvastatin calcium trihydrate were used as exemplar cardiovascular drugs and formulated into MN arrays using two biocompatible polymers, poly(vinylpyrrollidone) and poly(methylvinylether/maleic acid). Following fabrication, dissolution, mechanical testing, and determination of drug recovery from the MN arrays, in vitro drug delivery studies were undertaken, followed by HPLC analysis. All three drugs were successfully delivered in vitro across neonatal porcine skin, with similar permeation profiles achieved from both polymer formulations. An average of 126.3 ± 18.1 μg of atorvastatin calcium trihydrate was delivered, notably lower than the 687.9 ± 101.3 μg of lisinopril and 3924 ± 1011 μg of aspirin, because of the hydrophobic nature of the atorvastatin molecule and hence poor dissolution from the array. Polymer deposition into the skin may be an issue with repeat application of such a MN array, hence future work will consider more appropriate MN systems for continuous use, alongside tailoring delivery to less hydrophilic compounds.

Microneedles: an innovative platform for gene delivery

The advent of microneedle (MN) technology has provided a revolutionary platform for the delivery of therapeutic agents, particularly in the field of gene therapy. For over 20 years, the area of gene therapy has undergone intense innovation and progression which has seen advancement of the technology from an experimental concept to a widely acknowledged strategy for the treatment and prevention of numerous disease states. However, the true potential of gene therapy has yet to be achieved due to limitations in formulation and delivery technologies beyond parenteral injection of the DNA. Microneedle-mediated delivery provides a unique platform for the delivery of DNA therapeutics clinically. It provides a means to overcome the skin barriers to gene delivery and deposit the DNA directly into the dermal layers, a key site for delivery of therapeutics to treat a wide range of skin and cutaneous diseases. Additionally, the skin is a tissue rich in immune sentinels, an ideal target for the delivery of a DNA vaccine directly to the desired target cell populations. This review details the advancement of MN-mediated DNA delivery from proof-of-concept to the delivery of DNA encoding clinically relevant proteins and antigens and examines the key considerations for the improvement of the technology and progress into a clinically applicable delivery system.

Implementation of Selective Packet Destruction on Wireless Open-Access Research Platform

Interesting wireless networking scenarios exist wherein network services must be guaranteed in a dynamic fashion for some priority users. For example, in disaster recovery, members need to be able to quickly block other users in order to gain sole use of the radio channel. As it is not always feasible to physically switch off other users, we propose a new approach, termed selective packet destruction (SPD) to ensure service for priority users. A testbed for SPD has been created, based on the Rice University Wireless open-Access Research Platform and been used to examine the feasibility of our approach. Results from the testbed are presented to demonstrate the feasibility of SPD and show how a balance between performance and acknowledgement destruction rate can be achieved. A 90% reduction in TCP & UDP traffic is achieved for a 75% MAC ACK destruction rate.