An Induced Natural Selection Heuristic for Finding Optimal Bayesian Experimental Designs

Bayesian optimal experimental design has immense potential to inform the collection of data so as to subsequently enhance our understanding of a variety of processes. However, a major impediment is the difficulty in evaluating optimal designs for problems with large, or high-dimensional, design spaces. We propose an efficient search heuristic suitable for general optimisation problems, with a particular focus on optimal Bayesian experimental design problems. The heuristic evaluates the objective (utility) function at an initial, randomly generated set of input values. At each generation of the algorithm, input values are "accepted" if their corresponding objective (utility) function satisfies some acceptance criteria, and new inputs are sampled about these accepted points. We demonstrate the new algorithm by evaluating the optimal Bayesian experimental designs for the previously considered death, pharmacokinetic and logistic regression models. Comparisons to the current "gold-standard" method are given to demonstrate the proposed algorithm as a computationally-efficient alternative for moderately-large design problems (i.e., up to approximately 40-dimensions)

Evolutionary quantitative genetics of juvenile body size in a population of feral horses reveals sexually antagonistic selection

This is the author accepted manuscript. The final version is available from Springer via the DOI in this record.Inter-individual variation in juvenile body size can have important consequences for individual fitness, population dynamics, and adaptive evolution. In wild vertebrate populations, larger juvenile size is usually expected to be selected for. However, understanding how such selection may translate into adaptive evolution requires an understanding of the genetic underpinnings of early development and the factors modulating selection. In this study, we characterised the genetic basis of and selection pressures acting upon juvenile body size in a large insular population of feral horses on Sable Island, Canada, to gain insights into the evolution of juvenile body size in wild vertebrate populations. We used pedigree-based quantitative genetic ‘animal models’ to quantify the sources of phenotypic variation in withers-knee length, and assessed the influence of maternal age, sex, and temporal (birth year) and spatial environmental heterogeneity in modulating overwinter survival selection. We found that withers-knee length is moderately heritable and that there was a significant positive genetic correlation between males and females. There was no indication of directional selection in a pooled-sex analysis, but we did find evidence for significant sexually antagonistic selection, with a tendency for smaller body size to be favoured in males and larger body size to be favoured in females. These results suggest that juvenile body size has the potential to evolve in this population, and that selection on juvenile size may play an important role in modulating sex-specific contributions to population dynamics. However, our results also suggest that there is unlikely to be evolutionary change in the mean body size of Sable Island foals.Natural Sciences and Engineering Research Council of CanadaCanada Foundation for InnovationRoyal SocietyUniversity of Exete

Mechanical nociceptive threshold testing in Bos indicus bull calves

The aim of this prospective, controlled, randomised trial was to develop a technique for mechanical nociceptive threshold testing (NTT) to assess pain in Bos indicus bull calves undergoing surgical castration. Analgesia was provided by 0.5 mg/kg subcutaneous (SC) meloxicam (M) and/or 2 mg/kg of intra-testicular and SC (at the surgery sites) lidocaine (L). Forty-eight Brahman bull calves at 6–8 months of age were divided into six study groups, each with eight animals: no surgery control; surgical castration (C) without analgesia; C and Mpre-op; C and Mpost-op; C, L and Mpost-op; C and L. Mechanical NTT was performed the day before surgery (Day –1) and on Days 1, 2, 6, 10 and 13 after surgery. A handheld manual pneumatic device with a 1-mm (diameter) blunt pin was used to deliver a mechanical stimulus to a maximum of 27 Newtons either side of the most dorsal aspect of the sacrum. The most frequent responses to the mechanical stimulus were lifting or kicking of the leg on the same side as the stimulus (31%) and stepping away from the stimulus (24.9%). Data were analysed with a mixed effect linear model with the nociceptive threshold (NT) as the response variable and day and analgesic treatment as predictors (P < 0.05 was considered significant). For all groups, there was a trend towards decreasing NT over the study period but there were no significant differences between groups. Step down model selection with day, batch and treatment terms revealed a significant effect of day (P < 0.001) and batch (P = 0.007). Mechanical NTT for assessment of pain in Bos indicus bull calves requires further refinement to determine if this is a useful method of pain assessment

Designing group dose-response studies in the presence of transmission

Available online 25 July 2018Dose-response studies are used throughout pharmacology, toxicology and in clinical research to determine safe, effective, or hazardous doses of a substance. When involving animals, the subjects are often housed in groups; this is in fact mandatory in many countries for social animals, on ethical grounds. An issue that may consequently arise is that of unregulated between-subject dosing (transmission), where a subject may transmit the substance to another subject. Transmission will obviously impact the assessment of the dose-response relationship, and will lead to biases if not properly modelled. Here we present a method for determining the optimal design – pertaining to the size of groups, the doses, and the killing times – for such group dose-response experiments, in a Bayesian framework. Our results are of importance to minimising the number of animals required in order to accurately determine dose-response relationships. Furthermore, we additionally consider scenarios in which the estimation of the amount of transmission is also of interest. A particular motivating example is that of Campylobacter jejuni in chickens. Code is provided so that practitioners may determine the optimal design for their own studies.David J. Price, Nigel G. Bean, Joshua V. Ross, Jonathan Tuk

An induced natural selection heuristic for finding optimal Bayesian experimental designs

Abstract not avialableDavid J. Price, Nigel G. Bean, Joshua V. Ross, Jonathan Tuk

Mitigation of electroencephalographic and cardiovascular responses to castration in Bos indicus bulls following the administration of either lidocaine or meloxicam

Objective To investigate the mitigating effects of administration of local or systemic meloxicam on the electroencephalographic (EEG) and cardiovascular responses during surgical castration of Bos indicus bull calves. Study design Prospective, randomized, experimental study. Animals Thirty-six 6–8 month-old Bos indicus bull calves, with a mean ± standard deviation weight of 237 ± 19 kg. Methods Animals were randomly allocated to three groups of 12 (group L, 260 mg of 2% lidocaine subcutaneously and intratesticularly 5 minutes prior to castration; group M, 0.5 mg kg−1 of meloxicam subcutaneously 30 minutes prior to castration; group C, no pre-operative analgesia administered). Anaesthesia was induced and maintained with halothane (0.9–1.1%) in oxygen. Electroencephalogram, heart rate (HR) and mean blood pressure (MAP) were recorded for 300 seconds prior to (baseline, B) and from the start of surgery (first testicle incision, T1). HR and MAP were compared at 10 second intervals for 90 seconds from the start of T1. Median frequency (F50), spectral edge frequency (F95) and total power of the EEG (Ptot) were analysed using area under the curve comparing T1 to B. Results All EEG variables were significantly different between B and T1 (p ≤ 0.0001). No differences in F50 were found between groups during T1 (p = 0.6491). F95 and Ptot were significantly different between group L and groups C and M during T1 (p = 0.0005 and 0.0163, respectively). There were transient significant changes in HR and MAP in groups L and M compared to group C during the 20–50 second periods. Conclusions The EEG changes indicate nociceptive responses in all three groups during surgical castration, greater in group L compared to groups C and M. Both analgesics attenuated the peracute cardiovascular response. Lidocaine and meloxicam administered prior to castration attenuated these responses in Bos indicus bull calves. Clinical relevance These findings provide support for the pre-operative administration of lidocaine and potentially meloxicam for castration in Bos indicus bull calves

On the efficient determination of optimal Bayesian experimental designs using ABC: a case study in optimal observation of epidemics

We present a new method for determining optimal Bayesian experimental designs, which we refer to as ABCdE. ABCdE uses Approximate Bayesian Computation to calculate the utility of possible designs. For problems with a low-dimensional design space, it evaluates the designs’ utility in less computation time compared to existing methods. We apply ABCdE to stochastic epidemic models. Optimal designs evaluated using ABCdE are compared to those evaluated using existing methods for the stochastic death and susceptible–infectious (SI) models. We present the Bayesian optimal experimental designs for the susceptible–infectious–susceptible (SIS) model using ABCdE.David J. Price, Nigel G. Bean, Joshua V. Ross, Jonathan Tuk

Gender-specific effects of COVID-19 lockdowns on scientific publishing productivity: Impact and resilience

Available online 3 February 2023Rationale: The SARS-CoV2 pandemic led to drastic social restrictions globally. Early data suggest that women in science have been more adversely affected by these lockdowns than men, with relatively fewer scientific articles authored by women. However, these observations test broad populations with many potential causes of disparity. Australia presents a natural experimental condition where several states of similar demographics and disease impact had differing approaches in their social isolation strategies. The state of Victoria experienced 280 days of lockdowns from 2020 to 2021, whereas the comparable state of New South Wales experienced 107 days, most of these in 2021, and other states even fewer restrictions. Objective and methods: To assess how the gender balance changed in Australian biomedical publishing with the lockdowns, we created a custom workflow to analyse PubMed data from more than 120,000 published articles submitted in 2019–2021 from Australian authors. Results: Broadly, Australian women have been incredibly resilient to the challenges faced by the lockdowns. There was an increase in the number of published articles submitted in 2020 that was equally due to women as men, including from Victoria. On the other hand, articles specifically addressing COVID-19 were significantly less likely to be authored by women than those on other topics, a finding not likely due to particular gender imbalance in virology or viral epidemiology, since publications on HIV followed similar patterns to previous years. By 2021, this imbalance had reversed, with more COVID-19-related papers authored by women than men. Conclusions: These data suggest women from Victoria were less able to rapidly transition to new research early in the pandemic but had accommodated to the new conditions by 2021. This work indicates we need strategies to support women in science as the pandemic continues and to continue to monitor the situation for its impact on vulnerable groups.M. Ryan, J. Tuke, M.R. Hutchinson, S.J. Spence

Broad changes in body mass index between age 10 and adulthood are associated with type 2 diabetes risk independently of adult body mass index

 This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record Diabetes Research and Wellness FoundationDiabetes UKEuropean Foundation for the Study of Diabete