Pharmacogenetics of warfarin - is testing clinically indicated?

Pharmacogenetics is genetic testing to optimise prescribing for individual patients. Warfarin is a potential candidate for pharmacogenetic testing as it is commonly used, has a narrow therapeutic window and its mechanism of action and elimination pathways involve receptors and enzymes that are polymorphic. Polymorphism is found in vitamin K epoxide reductase and cytochrome P450 2C9. Pharmacogenetic testing is not yet routine because alone it does not predict all the variability in a patient's response to warfarin so its contribution to improved clinical outcomes is uncertain

Development of a method to identify foot strike on an arena surface: application to jump landing

Foot strike can be difficult to determine using kinematics alone, particularly when studying equine activities on more compliant surfaces, so this study was done with the aim of developing and validating a method to determine foot strike on an arena surface that can be used in conjunction with kinematics alone, and of applying the method in the context of measuring foot strike during jump landing on an arena surface. A low-cost contact mat was developed. The timing of the contact mat switching ‘on’ was compared to the timing of a force platform onset of 20 N, load and loading rate at foot strike. Two groups of 25 participants were used in two separate studies to validate the contact mat: the first measured the difference in timing with respect to two different activities (running and stepping down from a box), and the second measured the difference in timing with respect to 1- and 2-cm depths of an arena surface during running. In a third study, the mat was used to measure leading limb foot strike of six horses during jump landing, and these data were compared to kinematics from a palmar marker on the hoof wall. All data were recorded at 500 Hz. A consistent difference in delay was found between the mat and force platform onset, and as a result, no significant differences (P>0.05) in timing delay between different loading rates or depths were found. During jump landing, foot strike (determined from the mat) occurred after the vertical velocity minima and the acceleration maxima for the hoof marker, but it occurred before the point where the rate of vertical displacement began to reduce. In conclusion, further work is needed to enhance these techniques, but these preliminary results indicate that this method may be effective in determining foot strike for field-based applications

Demographic changes in UK rescue centre dog population between 2014 and 2018

Rescue centers remain a common means of rehoming a dog. There is a paucity of research into the composition of rescue center populations and its potential reflection of increased popularity of brachycephalic breeds. The study investigated changes in rescue center demographics from 2015 to 2018, compared to the wider dog population. Dogs on 16 rehoming centers’ websites were recorded weekly from June 2015 for 8 weeks and replicated from June 2018. Data were collected on 1793 dogs across the centers. Over 50% of which were classified as purebred in both years. Over 80% of the dogs were categorized into 24 breeds or breed crosses. Dogs categorized as brachycephalic increased from 24 (2.76%) in 2015 to 48 (5.19%) in 2018. Subadult dogs (3–4 years) were most prevalent in both years. While sex, breed type, and age of the rehoming center population has remained relatively stable, breeds are changing. Whilst low, brachycephalic numbers doubled in 3 years, mirroring their rising popularity within the UK, impacting on rehoming centers and prospective new owners with additional costs of brachycephalic obstructive airway syndrome surgery

Mannan oligosaccharide prepartum supplementation: effects on dairy cow colostrum quality and quantity

Providing the neonatal calf with a sufficient quantity and quality of colostrum may optimise future health, performance and reduce the risk of morbidity. A 6-month double blind trial with 80 prepartum dairy cows was conducted to determine if supplementation with mannan oligosaccharide (MOS) influences colostrum quality, quantity and subsequent calf performance. The Holstein cross Friesian 80 cows (no heifers) were allocated into a control and treatment group at the point of drying off by previous lactation number and yield. The control and treatment group were fed the same commercial standard dry cow diet throughout the trial supplemented with a mineral concentrate without or with 1.33% MOS, respectively. Cows were milked out of colostrum within 40 min of calving prior to calf suckling, weight was recorded. Mannan oligosaccharide fed cows produced significantly more colostrum on first milking (7.5 kg, SEM±0.69) compared with cows fed without MOS (5.6 kg, SEM±0.43). The immunoglobulin G (IgG) concentrations (control 53.7 IgG g/l, SEM±5.8 and MOS of 42.7 IgG g/l, SEM±4.9) and total mass of IgG did not differ between treatments. No significant observable MOS-derived effect on calf health or weight gain occurred during the study

Intraoperative changes in blood coagulation and thrombelastographic monitoring in liver transplantation

The blood coagulation system of 66 consecutive patients undergoing consecutive liver transplantations was monitored by thrombelastograph and analytic coagulation profile. A poor preoperative coagulation state, decrease in levels of coagulation factors, progressive fibrinolysis, and whole blood clot lysis were observed during the preanhepatic and anhepatic stages of surgery. A further general decrease in coagulation factors and platelets, activation of fibrinolysis, and abrupt decrease in levels of factors V and VIII occurred before and with reperfusion of the homograft. Recovery of blood coagulability began 30-60 min after reperfusion of the graft liver, and coagulability had returned toward baseline values 2 hr after reperfusion. A positive correlation was shown between the variables of thrombelastography and those of the coagulation profile. Thrombelastography was shown to be a reliable and rapid monitoring system. Its use was associated with a 33% reduction of blood and fluid infusion volume, whereas blood coagulability was maintained without an increase in the number of blood product donors

Investigating the use of real-time data in nudging patients' Emergency Department (ED) attendance behaviour

This is the author accepted manuscript. The final version is available from the Society for Modeling and Simulation International via the URL in this record.Decision-making in healthcare is a complex process involving multiple stakeholders. One such stakeholder category is the intended users of the system itself – the patients. We present a study in which users use real-time hospital operations data to make attendance choices. The work was carried out with the Torbay & South Devon NHS Foundation Trust (TSDFT) and its network of Minor Injury Units (MIUs) and one Emergency Department (ED). The aim of this research was to provide information transparency on ED/MIU waiting times which would allow recipients, including, significantly, patients who are in need of urgent medical attention, to make informed decisions as to the facility that could best serve their needs. This work will contribute towards reducing pressure in ED by redistributing demand for minor ailments among the MIUs, since the MIUs have facilities for the treatment of minor injuries and the ED exists mainly for emergency and life-threating conditions.We would like to acknowledge the ESRC Impact Acceleration Account on Project Co-creation for the project on “Systems Modelling and Computer Simulation of Urgent and Emergency Care in Torbay & South Devon"

Charge asymmetries of top quarks at hadron colliders revisited

A sizeable difference in the differential production cross section of top- compared to antitop-quark production, denoted charge asymmetry, has been observed at the Tevatron. The experimental results seem to exceed the theory predictions based on the Standard Model by a significant amount and have triggered a large number of suggestions for "new physics". In the present paper the Standard Model predictions for Tevatron and LHC experiments are revisited. This includes a reanalysis of electromagnetic as well as weak corrections, leading to a shift of the asymmetry by roughly a factor 1.1 when compared to the results of the first papers on this subject. The impact of cuts on the transverse momentum of the top-antitop system is studied. Restricting the ttbar system to a transverse momentum less than 20 GeV leads to an enhancement of the asymmetries by factors between 1.3 and 1.5, indicating the importance of an improved understanding of the $t\bar t$-momentum distribution. Predictions for similar measurements at the LHC are presented, demonstrating the sensitivity of the large rapidity region both to the Standard Model contribution and effects from "new physics".Comment: 23 pages. Final version to appear in JHE

Electroweak corrections to W-boson pair production at the LHC

Vector-boson pair production ranks among the most important Standard-Model benchmark processes at the LHC, not only in view of on-going Higgs analyses. These processes may also help to gain a deeper understanding of the electroweak interaction in general, and to test the validity of the Standard Model at highest energies. In this work, the first calculation of the full one-loop electroweak corrections to on-shell W-boson pair production at hadron colliders is presented. We discuss the impact of the corrections on the total cross section as well as on relevant differential distributions. We observe that corrections due to photon-induced channels can be amazingly large at energies accessible at the LHC, while radiation of additional massive vector bosons does not influence the results significantly.Comment: 29 pages, 15 figures, 4 tables; some references and comments on \gamma\gamma -> WW added; matches version published in JHE