Translating pharmacogenetics and pharmacogenomics to the clinic: progress in human and veterinary medicine

As targeted personalized therapy becomes more widely used in human medicine, clients will expect the veterinary clinician to be able to implement an evidence-based strategy regarding both the prescribing of medicines and also recognition of the potential for adverse drug reactions (ADR) for their pet, at breed and individual level. This review aims to provide an overview of current developments and challenges in pharmacogenetics in medicine for a veterinary audience and to map these to developments in veterinary pharmacogenetics. Pharmacogenetics has been in development over the past 100 years but has been revolutionized following the publication of the human, and then veterinary species genomes. Genetic biomarkers called pharmacogenes have been identified as specific genetic loci on chromosomes which are associated with either positive or adverse drug responses. Pharmacogene variation may be classified according to the associated drug response, such as a change in (1) the pharmacokinetics; (2) the pharmacodynamics; (3) genes in the downstream pathway of the drug or (4) the effect of “off-target” genes resulting in a response that is unrelated to the intended target. There are many barriers to translation of pharmacogenetic information to the clinic, however, in human medicine, international initiatives are promising real change in the delivery of personalized medicine by 2025. We argue that for effective translation into the veterinary clinic, clinicians, international experts, and stakeholders must collaborate to ensure quality assurance and genetic test validation so that animals may also benefit from this genomics revolution

Spin gating electrical current

We use an aluminium single electron transistor with a magnetic gate to directly quantify the chemical potential anisotropy of GaMnAs materials. Uniaxial and cubic contributions to the chemical potential anisotropy are determined from field rotation experiments. In performing magnetic field sweeps we observe additional isotropic magnetic field dependence of the chemical potential which shows a non-monotonic behavior. The observed effects are explained by calculations based on the $\mathbf{k}\cdot\mathbf{p}$ kinetic exchange model of ferromagnetism in GaMnAs. Our device inverts the conventional approach for constructing spin transistors: instead of spin-transport controlled by ordinary gates we spin-gate ordinary charge transport.Comment: 5 pages, 4 figure

Correlation of Chemical and Physical Test Data for the Environmental Ageing of Tefzel (ETFE)

In a similar approach to that used for the previously issued correlation report for Coflon (CAPP/M.10), this report aims to identify any correlations between mechanical property changes and chemical/morphological changes for Tefzel, using information supplied in other MERL and TRI project reports (plus latest data which will be included in final reports for Phase 1). Differences identified with Coflon behaviour will be of scientific interest as well as appropriate to project applications, as Tefzel and Coflon are chemical isomers. Owing to the considerable chemical resistance of Tefzel, much of its testing so far has been based on mechanical properties. Where changes have occurred, chemical analysis can now be targeted more effectively. Relevant test data collated here include: tensile modulus and related properties, permeation coefficients, % crystallinity, and other observations where significant. Fluids based on methanol and amine (Fluid G), a mixture of methane, carbon dioxide and hydrogen sulphide gases plus an aqueous amine solution (Fluid F), and an aromatic oil mix of heptane, cyclohexane, toluene and I-propanol (Fluid 1) have affected Tefzel to varying degrees, and are discussed in some detail herein

Correlation of Chemical and Physical Test Data for the Environmental Ageing of Tefzel (ETFE)

In a similar approach to that used for the previously issued correlation report for Coflon (CAPP/M.10), this report aims to identify any correlations between mechanical property changes and chemical/morphological changes for Tefzel, using information supplied in other MERL and TRI project reports. Differences identified with Coflon behaviour will be of scientific interest as well as appropriate to project applications, as Tefzel and Coflon are chemical isomers. Owing to the considerable chemical resistance of Tefzel, much of its testing so far has been based on mechanical properties. Where changes have occurred, chemical analysis can now be targeted more effectively. Relevant test data collated here include: tensile modulus and related properties, permeation coefficients, % crystallinity, some crack growth resistance measurements, and other observations where significant. Fluids based on methanol and amine (Fluid G), a mixture of methane, carbon dioxide and hydrogen sulphide gases plus an aqueous amine solution (Fluid F), and an aromatic oil mix of heptane, cyclohexane, toluene and 1-propanol (Fluid I) have affected Tefzel to varying degrees, and are discussed in some detail herein

High Pressure Gas Permeation and Liquid Diffusion Studies of Coflon and Tefzel Thermoplastics

The life of fluid-carrying flexible or umbilical pipes during service at elevated temperatures and pressures depends inter alia on their resistance to attack by the fluids present and the rate at which these fluids are absorbed by the pipe lining materials. The consequences of fluid ingress into the thermoplastic lining could mean a) a reduction in its mechanical strength, to increase chances of crack formation and growth and thus a loss of integrity, b) the occurrence of permeation right through the lining material, with pressure build- up in the outer pipe wall construction (of flexible pipes) or chemical attack (from a hostile permeant) on outer layers of reinforcements. Therefore it is important within this project to have relevant permeation data for Coflon and Tefzel thermoplastics: the former is plasticised, the latter is not. A previous report (CAPP/M.2) described experimental equipment and techniques used by MERL when measuring high pressure (up to 5000 psi) gas permeation and liquid diffusion through thermoplastic samples cut from extruded bar or pipe, and provided the basic theory involved. Norsk Hydro are also performing gas permeation tests on pipe sections, at up to 100 bars (1450 psi) pressure or so, and reporting separately. Some comparisons between data from Norsk Hydro and MERL have been made herein. The tests should be considered as complementary, as the Norsk Hydro test has the obvious benefit of using complete pipe sections, whilst MERL can test at much higher pressures, up to 1000 bar if necessary. The sophisticated analytical measuring equipment of Norsk Hydro can distinguish the individual components of mixed gases and hence the various permeation-linked coefficients whereas MERL, in using pressure increase at constant volume to determine permeation rate, is limited to obtaining single gas data, or apparent (or representative) coefficients for a mixed gas as a whole. Except for the initial fluid diffusion data for Tefzel described in CAPP/M.2, the present report covers all aspects of fluid permeation and diffusion for Coflon and Tefzel, including all the pen-neation data accumulated in the project to date. Test gases have mainly been methane (CH4) and carbon dioxide (CO2). More high pressure (HP) gas permeation tests have been performed since the last issue of this report, most being concerned with changes in permeation characteristics brought about by ageing in various relevant fluids. This revision supersedes previous issues

Correlation of Chemical and Physical Test Data For the Environment Ageing of Coflon (PVDF)

This report aims to identify correlations between mechanical property changes and chemical/morphological structure changes for Coflon. It is intended both to illustrate the overall methodology and to indicate the testing that needs to be undertaken in order to obtain correlations. Many fluid exposures have now been carried out on Coflon during the project and many data generated as a result. The report summarises the changes observed in mechanical and physical properties and relates these as well as possible to the chemistry thought to be occurring during ageing. For this purpose, data have been collated from already-issued MERL and TRI technical and progress reports. Most of the mechanical testing of aged testpieces has been performed soon after the completion of the exposure; however, there is of necessity a delay in obtaining chemical analysis of the same testpieces, so that more physical than chemical data are shown. Three fluids have so far caused measurable deterioration of Coflon, these being: methanol (Fluid A), a methanol and amine mixture (Fluid G), and a mixture of methane, carbon dioxide gas and hydrogen sulphide gas plus aqueous amine (Fluid F). Only the effects of these fluids will be dealt with in any detail in this report, although other fluids are assessed to give relevant background information. Relevant test data collated here include: tensile modulus and related properties, mode of sample failure at break, fracture toughness, fatigue crack growth rate and resistance, stress relaxation rate, permeation coefficients, % crystallinity and molecular weight distributions together with changes in fluorine levels, and other observations where appropriate. However, not all of these were obtained for every ageing condition. Because of the wide range of tests employed, and the different ways in which their results are obtained, the following section has been included to serve as a background for making comparisons