Exploring stable-based behaviour and behaviour switching for the detection of bilateral pain in equines

Efficient and sensitive animal pain detection approaches are increasingly studied with the goal of improving animal welfare and monitoring the efficacy of treatment and rehabilitation. The aim of this study was to determine the potential of various behaviours as sensitive indicators of subtle inflammation states in equines. The long-term goal of this research is to understand how to objectively and remotely classify behaviours that are associated with inflammation using wearable inertial sensor technologies. This study represents a proof-of concept investigation to ascertain what behavioural indices might be important in long-term monitoring of mild bilateral inflammation and recovery with a view to translating the approach to a technology-enabled remote monitoring paradigm. Bilateral synovitis of the intercarpal joints was induced in seven equines using lipopoly saccharide (0.25 ng) at time zero. The horses were confined to stables and monitored intermittently over seven days by stable-fixed video cameras. White blood cell count, carpal circumference and food availability were recorded across the study. An ethogram was created to manually annotate behaviours from video footage following lameness induction at seven different timepoints across a 1-week period. Behaviour data were processed extracting the duration, frequency and variability of behaviours. One-way repeated measures ANOVA revealed a significant time effect for white blood cell count and behaviour switching. There were no significant changes in carpal circumferences and heart rate measures over the sampling period. Food availability appears to be an important contextual factor that should be considered in pain-related behavioural studies. We conclude that behaviour variability may be a promising indicator of subtle bilateral inflammation which should be further explored in larger controlled trials and different pain presentations. Future work will seek to optimise grouping of behaviours associated with inflammation that can be detected using wearable technologies for future remote monitoring protocols

Defining the clinical and cognitive phenotype of child savants with autism spectrum disorder

Objective: Whilst savant syndrome is most commonly observed in individuals with Autism Spectrum Disorder (ASD), it has historically been associated with intellectual impairment, and little is known about the clinical and cognitive characteristics of intellectually able individuals with ASD and savant skills. Methods: Participants with ASD and validated savant skills were compared with age and intelligence matched non-savants with ASD using a range of diagnostic and standardised tests. Results: Although the analysis of the clinical data revealed few differences between the groups, striking differences emerged during cognitive testing. Children with savant skills exhibited highly superior working memory and their scores on tests of analytic skills were also superior to those of non-savants. Conclusion: We propose that obsessionality, focused attention, superior working memory and analytic skills facilitate veridical mapping and pattern perception abilities characteristic in savant syndrome

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Exploring the potential of wearable technology to impact equine movement analysis in the applied field

The digital age has given rise to an explosion of ambient and wearable devices facilitating the collection of ecologically valid movement data. Many equine researchers have highlighted the capability of wearable technology to improve the reliability and validity of objective equine gait analysis, particularly with respect to lameness assessment. This thesis leverages the learning accrued from the integration of technology into healthcare and athletic performance management in the applied human field, to understand how best to progress the developing field of objective equine monitoring and movement analysis. The aim of the thesis was to explore the translational research space by a) focusing on the stakeholders who would potentially be the end-users of such technologies, and b) using wearable technology to collect equine movement data where it would ultimately be used i.e. in the applied setting. A bilateral lameness model was employed as the use case for exploring the potential of behaviour, locomotor and postural sway data - derived from video and a single accelerometer - to provide meaningful information on inflammation and recovery. Research presented outlines that expert equine stakeholders perceived that current technological offerings did not exceed their value threshold in providing additional equine health and performance insights. Additionally, it was evident from chapters Five, Six and Eight that variability of movement as a discriminator between normal and abnormal joint inflammation merits further attention. Behaviour switching, variability of acceleration during locomotion and amplitude of postural sway were shown to be statistically different in inflamed versus normal states. This project demonstrated the feasibility of harvesting a variety of meaningful movement parameters using a single accelerometer in the applied field. Future work should focus on knowledge exchange activities that could enrich the development of fit-for-purpose technologies that can add value to existing equine management practices

Irish Equine Industry Stakeholder Perspectives of Objective Technology for Biomechanical Analyses in the Field

Wearable sensing technologies are increasingly used in human and equine gait research to improve ecological validity of research findings. It is unclear how these tools have penetrated the equine industry or what perspectives industry stakeholders&rsquo; hold in relation to these relatively new devices. Semi-structured interviews were conducted with Irish equine industry stakeholders to understand their perception of objective tools for biomechanical analysis in the field. The study participants came from professional/elite backgrounds in both the sport horse (n = 6) and thoroughbred (n = 6) sectors. The interview data were analysed using thematic analysis, resulting in four analytical themes. The first theme conveys the importance of tacit knowledge and experience in the holistic analysis of a horse. Theme two highlights that the perfect horse does not exist therefore, equine athlete management is complex and requires a multi-layered problem-solving approach. Theme three describes an awareness among stakeholders of technologies, however they are sceptical of their value. The final theme identified that one of the key barriers to technology adoption is the economic value of the horse and the cost of implementing technology herd-wide. Our findings highlight the need for a user-centred design in this domain, which requires greater consultation and learning between technology developers and equine stakeholders to develop fit-for-purpose analysis and monitoring tools

The Feasibility of Equine Field-Based Postural Sway Analysis Using a Single Inertial Sensor

(1) Background: Postural sway is frequently used to quantify human postural control, balance, injury, and neurological deficits. However, there is considerably less research investigating the value of the metric in horses. Much of the existing equine postural sway research uses force or pressure plates to examine the centre of pressure, inferring change at the centre of mass (COM). This study looks at the inverse, using an inertial measurement unit (IMU) on the withers to investigate change at the COM, exploring the potential of postural sway evaluation in the applied domain. (2) Methods: The lipopolysaccharide model was used to induce transient bilateral lameness in seven equines. Horses were monitored intermittently by a withers fixed IMU over seven days. (3) Results: There was a significant effect of time on total protein, carpal circumference, and white blood cell count in the horses, indicating the presence of, and recovery from, inflammation. There was a greater amplitude of displacement in the craniocaudal (CC) versus the mediolateral (ML) direction. A significant difference was observed in the amplitude of displacement in the ML direction between 4–12 h and 168 h. (4) Conclusions: The significant reduction in ML displacement during the acute inflammation period alongside greater overall CC displacement may be a compensatory behaviour for bilateral lameness

The Feasibility of Equine Field-Based Postural Sway Analysis Using a Single Inertial Sensor

(1) Background: Postural sway is frequently used to quantify human postural control, balance, injury, and neurological deficits. However, there is considerably less research investigating the value of the metric in horses. Much of the existing equine postural sway research uses force or pressure plates to examine the centre of pressure, inferring change at the centre of mass (COM). This study looks at the inverse, using an inertial measurement unit (IMU) on the withers to investigate change at the COM, exploring the potential of postural sway evaluation in the applied domain. (2) Methods: The lipopolysaccharide model was used to induce transient bilateral lameness in seven equines. Horses were monitored intermittently by a withers fixed IMU over seven days. (3) Results: There was a significant effect of time on total protein, carpal circumference, and white blood cell count in the horses, indicating the presence of, and recovery from, inflammation. There was a greater amplitude of displacement in the craniocaudal (CC) versus the mediolateral (ML) direction. A significant difference was observed in the amplitude of displacement in the ML direction between 4–12 h and 168 h. (4) Conclusions: The significant reduction in ML displacement during the acute inflammation period alongside greater overall CC displacement may be a compensatory behaviour for bilateral lameness

Discovery of Small Molecules That Induce Lysosomal Cell Death in Cancer Cell Lines Using an Image-Based Screening Platform

The lysosomal cell death (LCD) pathway is a caspase 3-independent cell death pathway that has been suggested as a possible target for cancer therapy, making the development of sensitive and specific high-throughput (HT) assays to identify LCD inducers highly desirable. In this study, we report a two-step HT screening platform to reliably identify such molecules. First, using a robust HT primary screen based on propidium iodide uptake, we identified compounds that kill through nonapoptotic pathways. A phenotypic image-based assay using a galectin-3 (Gal-3) reporter was then used to further classify hits based on lysosomal permeabilization, a hallmark of LCD. The identification of permeabilized lysosomes in our image-based assay is not affected by changes in the lysosomal pH, thus resolving an important limitation in currently used methods. We have validated our platform in a screen by identifying 24 LCD inducers, some previously known to induce LCD. Although most LCD inducers were cationic amphiphilic drugs (CADs), we have also identified a non-CAD LCD inducer, which is of great interest in the field. Our data also gave new insights into the biology of LCD, suggesting that lysosomal accumulation and acid sphingomyelinase inhibition are not sufficient or necessary for the induction of LCD. Overall, our results demonstrate a robust HT platform to identify novel LCD inducers that will also be very useful for gaining deeper insights into the molecular mechanism of LCD induction

An investigation into human pandemic influenza virus (H1N1) 2009 on an Alberta swine farm

On May 2, 2009 the Canadian Food Inspection Agency notified the World Organization for Animal Health that an emerging novel influenza A virus (pandemic H1N1 2009) had been confirmed on a swine farm in Alberta. Over a 4-week period pigs in this farrow-to-finish operation were clinically affected by respiratory disease consistent with an influenza A virus infection and the presence of active viral infection was confirmed in all production areas by real-time polymerase chain reaction (RT-PCR). Despite clinical recovery of animals, there was reluctance by purchasers to receive animals from this operation due to concerns about the effect on both domestic and international markets. The owner decided to depopulate the entire herd due to impending welfare issues associated with overcrowding and economic concerns resulting from the inability to market these animals. Carcasses were rendered or composted and did not enter the human food or animal feed chain. The source of virus in this herd was determined to be an infected human. Zoonotic transmission to 2 individuals responding to the outbreak was suspected and recommendations to prevent occupational exposure are discussed