Ethics, Genetic Technologies and Equine Sports: The Prospect of Regulation of a Modified Therapeutic Use Exemption Policy

This article critically reviews the current availability and selected use of genetic technologies for horses, before undertaking an ethical evaluation of current practice and regulatory positions in comparative relation to debates surrounding genetic testing, pre-implantation genetic testing and gene editing in humans. We argue that genetic testing for hereditary disorders is not only justified but should be encouraged on welfare grounds and that genetic testing for performance traits is ethically permissible based on a restricted imperative to genetically edit horses and horse embryos to reduce genetic predisposition to disease and injury. Given the current state of the science, where the effects of gene editing on health and welfare are currently undetermined, space is created for an analytical distinction between equine gene editing for ‘treatment’ and for ‘enhancement’. Gene editing is only justified for purposes of correcting/preventing disease and injury. Current regulation is challenged by apparently conflicting welfare-based ethical imperatives with respect to welfare-based gene editing. We propose modifications to the blanket bans on gene editing with a case-by-case assessment of applications to permit gene editing, based on best welfare interests underwritten by the aim of facilitating fair sport that adapt WADAs International Standard for Therapeutic Use Exemptions, adding an important reporting element. We reject the use of gene editing to obtain currently prohibited competitive advantages. In order to safeguard the welfare of human and equine athletes, we argue that regulatory institutions should urgently collaborate to develop cross-sport international regulations for the use of gene editing, including obligatory reporting of data about the health and welfare of genetically edited horses

Exponential sum approximations for t−βt^{-\beta}

Given $\beta>0$ and $\delta>0$, the function $t^{-\beta}$ may be approximated for $t$ in a compact interval $[\delta,T]$ by a sum of terms of the form $we^{-at}$, with parameters $w>0$ and $a>0$. One such an approximation, studied by Beylkin and Monz\'on, is obtained by applying the trapezoidal rule to an integral representation of $t^{-\beta}$, after which Prony's method is applied to reduce the number of terms in the sum with essentially no loss of accuracy. We review this method, and then describe a similar approach based on an alternative integral representation. The main difference is that the new approach achieves much better results before the application of Prony's method; after applying Prony's method the performance of both is much the same.Comment: 18 pages, 5 figures. I have completely rewritten this paper because after uploading the previous version I realised that there is a much better approach. Note the change to the title. Have included minor corrections following revie

Ethics, evidence based sports medicine, and the use of platelet rich plasma in the English Premier League

The use of platelet rich plasma (PRP) as a novel treatment is discussed in the context of a qualitative research study comprising 38 interviews with sports medicine practitioners and other stakeholders working within the English Premier League during the 2013-16 seasons. Analysis of the data produced several overarching themes: conservatism versus experimentalism in medical attitudes; therapy perspectives divergence; conflicting versions of appropriate evidence; subcultures; community beliefs/practices; and negotiation of medical decision-making. The contested evidence base for the efficacy of PRP is presented in the context of a broader professional shift towards evidence based medicine within sports medicine. Many of the participants while accepting this shift are still committed to casuistic practices where clinical judgment is flexible and does not recognize a context-free hierarchy of evidentiary standards to ethically justifiable practice. We also discuss a tendency in the data collected to consider the use of deceptive, placebo-like, practices among the clinician participants that challenge dominant understandings of informed consent in medical ethics. We conclude that the complex relation between evidence and ethics requires greater critical scrutiny for this emerging specialism within the medical community

Study on Doping Prevention: A map of Legal, Regulatory and Prevention Practice Provisions in EU 28

Historically, anti-doping efforts have focused on the detection and deterrence of doping in elite and competitive sport. There is, however, a growing concern that doping is occurring outside the organised sporting system; giving rise to the belief that the misuse of doping agents in recreational sport has become a societal problem and a public health issue that must be addressed. The EU Commission awarded a contract (EAC/2013/0617) to a Consortium to undertake this Study with the aim of developing the evidence-base for policies designed to combat doping in recreational sport. Fourteen internationally recognised experts shaped the Study which comprised (i) the collection of primary data through a structured survey, and (ii) secondary data through literature searches and website analysis. All 28 Member States participated in the information-gathering process. Specifically, this involved a systematic study of the ethical considerations, legal position, prevention research landscape, and current practise in relation to the prevention of doping in recreational sport. The Study provides a comprehensive overview of current practice and legislation as it applies to the prevention of doping and promotes and supports the sharing of best practices in the EU regarding the fight against doping in recreational sport. It concludes with seven recommendations for future action that focus on the need for a coordinated response in relation to the problems arising from doping in recreational sport

Trajectories through semantic spaces in schizophrenia and the relationship to ripple bursts

Human cognition is underpinned by structured internal representations that encode relationships between entities in the world (cognitive maps). Clinical features of schizophrenia-from thought disorder to delusions-are proposed to reflect disorganization in such conceptual representations. Schizophrenia is also linked to abnormalities in neural processes that support cognitive map representations, including hippocampal replay and high-frequency ripple oscillations. Here, we report a computational assay of semantically guided conceptual sampling and exploit this to test a hypothesis that people with schizophrenia (PScz) exhibit abnormalities in semantically guided cognition that relate to hippocampal replay and ripples. Fifty-two participants [26 PScz (13 unmedicated) and 26 age-, gender-, and intelligence quotient (IQ)-matched nonclinical controls] completed a category- and letter-verbal fluency task, followed by a magnetoencephalography (MEG) scan involving a separate sequence-learning task. We used a pretrained word embedding model of semantic similarity, coupled to a computational model of word selection, to quantify the degree to which each participant's verbal behavior was guided by semantic similarity. Using MEG, we indexed neural replay and ripple power in a post-task rest session. Across all participants, word selection was strongly influenced by semantic similarity. The strength of this influence showed sensitivity to task demands (category > letter fluency) and predicted performance. In line with our hypothesis, the influence of semantic similarity on behavior was reduced in schizophrenia relative to controls, predicted negative psychotic symptoms, and correlated with an MEG signature of hippocampal ripple power (but not replay). The findings bridge a gap between phenomenological and neurocomputational accounts of schizophrenia

Pharmacist-led management of chronic pain in primary care:results from a randomised controlled exploratory trial

To compare the effectiveness of pharmacist medication review, with or without pharmacist prescribing, with standard care, for patients with chronic pain

Financial Doping in the English Premier League

Whilst the relationship between money and success in elite sport is acknowledged, the exact nature, extent and implications of this relationship is one that has not been carefully examined. In this paper we have three main aims. Firstly, to provide empirical evidence of the extent that money buys success in the English Premier League. Secondly, to evaluate this evidence from a sports ethics perspective, and, finally, to discuss potential solutions to the problem. We argue that the evident performance advantage teams gain through financial investments is contrary to the spirit of sport as it undermines athletic excellence and the ‘sweet tension of uncertainty of outcome’ that is central to good competition. Consequently, financial investments in elite football ought to be regulated and controlled. We argue, however, that current attempts to do so (via Financial Fair Play Regulations) are inadequate as they focus on issues concerning financial health, rather than the health of the game in terms of spirit and fairness

Generating EQ-5D-5L health utility scores from BASDAI and BASFI : a mapping study in patients with axial spondyloarthritis using longitudinal UK registry data

Acknowledgements We are grateful to the staff of the British Society for Rheumatology Biologics Register in Axial Spondyloarthritis. Claudia Zabke, Maureen Heddle, Nafeesa Nazlee and Barry Morris, and to the recruiting staff at the clinical centres, details of which are available at: https://www.abdn.ac.uk/iahs/research/epidemiology/spondyloarthritis.php#panel1011. Funding The British Society for Rheumatology Biologics Register in Ankylosing. Spondylitis (BSRBR-AS) is funded by the British Society for Rheumatology (BSR), which in turn has received funding from the manufacturers of the biologic therapies included in the study (Abbvie, Pfizer and UCB). Pharmaceutical companies providing funds to BSR do not have a role in the oversight of the study, but they do receive advance notice of publications on which they can comment. They do not have access to the data collected but can request analyses of the data, for which additional funds are provided.Peer reviewedPublisher PD

Perspectives from the water: Utilizing fisher’s observations to inform SNE/ MA windowpane science and managemen

Within fisheries, stakeholders often have varying viewpoints regarding natural marine resources, and use different sets information to evaluate their condition. Evaluating a resource with different sets of information can lead to different conclusions. Windowpane flounder (Scophthalmus aquosus) are a managed finfish species in the northwest Atlantic whose regulations have the potential to limit harvest opportunities for target species. We analyzed commercial trip and catch information from video data to understand local densities of windowpane flounder in conjunction with fisheries independent surveys. Video monitoring data from three Rhode Island commercial fisher’s vessels and fisheries independent trawl survey data were analyzed to understand the geographic distribution of the stock as well as overlap with temporary closed areas. Biomass data from the fisheries-dependent and fisheries-independent surveys were combined with a spatial-temporal model that accounted for differences in catchability among vessels and spatial autocorrelation. A separate analysis of esti-mated discard rates with observer data was also conducted to determine how the distribution of windowpane discards in Southern New England compared to the distribution of model predicted windowpane abundance. In agreement with the fishermen’s observations, the temporary closed areas were not located where the highest densities of windowpane flounder occurred. The temporary closed areas, however, were located where the highest rates of discards occurred and thus where fishing had the greatest impact on the stock. The integration of verified fishery-dependent data with the scientific surveys has the potential to create a single set of information that is trusted by all user groups

Levosimendan for the prevention of acute organ dysfunction in sepsis

BACKGROUND Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis. METHODS We conducted a double-blind, randomized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis. Patients were randomly assigned to receive a blinded infusion of levosimendan (at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo in addition to standard care. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; maximum score, 20). Secondary outcomes included 28-day mortality, time to weaning from mechanical ventilation, and adverse events. RESULTS The trial recruited 516 patients; 259 were assigned to receive levosimendan and 257 to receive placebo. There was no significant difference in the mean (±SD) SOFA score between the levosimendan group and the placebo group (6.68±3.96 vs. 6.06±3.89; mean difference, 0.61; 95% confidence interval [CI], −0.07 to 1.29; P=0.053). Mortality at 28 days was 34.5% in the levosimendan group and 30.9% in the placebo group (absolute difference, 3.6 percentage points; 95% CI, −4.5 to 11.7; P=0.43). Among patients requiring ventilation at baseline, those in the levosimendan group were less likely than those in the placebo group to be successfully weaned from mechanical ventilation over the period of 28 days (hazard ratio, 0.77; 95% CI, 0.60 to 0.97; P=0.03). More patients in the levosimendan group than in the placebo group had supraventricular tachyarrhythmia (3.1% vs. 0.4%; absolute difference, 2.7 percentage points; 95% CI, 0.1 to 5.3; P=0.04). CONCLUSIONS The addition of levosimendan to standard treatment in adults with sepsis was not associated with less severe organ dysfunction or lower mortality. Levosimendan was associated with a lower likelihood of successful weaning from mechanical ventilation and a higher risk of supraventricular tachyarrhythmia. (Funded by the NIHR Efficacy and Mechanism Evaluation Programme and others; LeoPARDS Current Controlled Trials number, ISRCTN12776039.