Cosmic magnetism: The plasma physics of the recombining universe

This thesis presents an analytical and computational approach to modelling partially ionised, spatially-inhomogeneous and recombining plasmas. The specific context for this study is astrophysical plasmas, the early Universe in particular. Two models are investigated in detail: a magnetohydrodynamic (MHD) plasma model to simulate partially ionised plasmas; and a fully electromagnetic/kinetic model, used to study recombining plasmas. The first section further develops an existing computational model of a partially ionised plasma as a mixture of two cospatial fluids: an MHD plasma and a neutral gas. In order to model the interaction between the plasma and neutral gas populations ab initio, a collisional momentum exchange term was added to the momentum equation of each fluid. The model was used to investigate the combined response to different wave modes driven in the plasma or the neutral gas. The momentum coupling between the plasma and the neutral gas leads to complex interactions between the two populations. In particular, the propagation of plasma waves induces waves in the neutral gas by virtue of the collisional momentum exchange between the velocity fields of each fluid. This means that the normal wave modes of each independent fluid are modified to produce a combined, hybrid response, with the intriguing possibility that neutral gas can not only respond indirectly to magnetic fluctuations but also generate them via sound waves. This model is used to examine an existing observational method known as the ‘Chandrasekhar-Fermi method’ (CF53) for the diagnosis of magnetic fields in astrophysical plasmas. CF53 is commonly applied to objects such as nebulae and molecular clouds which are partially-ionised plasmas. It assumes that the gas motion can be used to infer the magnetic field strength, given coupling between Alfv´en waves in the plasma and the thermal motion of the neutral gas. Computational results show that this method may need to be refined, and that certain assumptions made should be re-evaluated. This is consistent with reports in the literature of CF53 under- or over-estimating the magnetic fields in objects such as molecular clouds. The second part of this thesis concentrates on the non-equilibrium evolution of magnetic field structures at the onset of the large-scale recombination of an inhomogeneouslyionised plasma, such as the Universe was during the epoch of recombination. The conduction currents sustaining the magnetic structure will be removed as the charges comprising them combine into neutrals. The effect that a decaying magnetic flux has on the acceleration of remaining charged particles via the transient induced electric field is considered. Since the residual charged-particle number density is small as a result of decoupling, the magnetic and electric fields can be considered essentially to be imposed, neglecting for now the feedback from any minority accelerated population. The electromagnetic treatment of this phase transition can produce energetic electrons scattered throughout the Universe. Such particles could have a significant effect on cosmic evolution in several ways: (i) their presence could influence the overall physics of the recombination era; and (ii) a population of energetic particles might lend a Coulomb contribution to localized gravitational collapse. This is confirmed by a numerical simulation in which a magnetic domain is modelled as a uniform field region produced by a thin surrounding current sheet. The imposed decay of the current sheet simulates the formation of neutrals characteristic of the decoupling era, and the induced electric field accompanying the magnetic collapse is able to accelerate ambient stationary electrons (that is, electrons not participating in the current sheet) to energies of up to order 10keV. This is consistent with theoretical predictions

A description of veterinary eliminations within British National Endurance rides in the competitive season of 2019

Veterinary eliminations within the equestrian sport of endurance have predominantly been evaluated based on data from international competitions. However, in order to take part in international competition, each horse and rider must qualify by completing rides under their national federation. The aim of this study was to analyse the competitive data and veterinary eliminations, specifically lameness, from competitions run by the British governing body of endurance: Endurance GB, during the 2019 competitive season. Competitive results for 765 ride starts from seven different ride venues were evaluated; 81.6% (n=624) horses successfully completed the rides, with the remaining 18.4% (n=141) failing to complete the ride. The majority of horses that were unsuccessful were eliminated for lameness at veterinary inspections (n=83; 58.9%). Horses competing in single loop rides (up to 55 km rides) had a success rate of 88.6% (n=624), in contrast, horses competing in rides of three loops or more (>80 km rides) reported a decreased success rate of 61.8% (n=81). Hindlimb lameness was identified more frequently (n=50; 60.2%) compared with forelimb lameness (n=33; 39.8%). Further consideration should be given to the differences between single loop rides, where a higher percentage are presented to the veterinary panel as lame prior to the start, and multi loop rides, where a higher percentage of horses are eliminated lame during the ride and potential risk factors for the increased prevalence of hindlimb lameness observed

Comparison of loop-mediated isothermal amplification (LAMP) and PCR for the diagnosis of infection with Trypanosoma brucei ssp. in equids in The Gambia

Introduction: Infection of equids with Trypanosoma brucei (T. brucei) ssp. is of socioeconomic importance across sub-Saharan Africa as the disease often progresses to cause fatal meningoencephalitis. Loop-mediated isothermal amplification (LAMP) has been developed as a cost-effective molecular diagnostic test and is potentially applicable for use in field-based laboratories. Part I: Threshold levels for T. brucei ssp. detection by LAMP were determined using whole equine blood specimens spiked with known concentrations of parasites. Results were compared to OIE antemortem gold standard of T. brucei-PCR (TBR-PCR). Results I: Threshold for detection of T. brucei ssp. on extracted DNA from whole blood was 1 parasite/ml blood for LAMP and TBR-PCR, and there was excellent agreement (14/15) between tests at high (1 x 103/ml) concentrations of parasites. Detection threshold was 100 parasites/ml using LAMP on whole blood (LWB). Threshold for LWB improved to 10 parasites/ml with detergent included. Performance was excellent for LAMP at high (1 x 103/ml) concentrations of parasites (15/15, 100%) but was variable at lower concentrations. Agreement between tests was weak to moderate, with the highest for TBR-PCR and LAMP on DNA extracted from whole blood (Cohen’s kappa 0.95, 95% CI 0.64–1.00). Part II: A prospective cross-sectional study of working equids meeting clinical criteria for trypanosomiasis was undertaken in The Gambia. LAMP was evaluated against subsequent TBR-PCR. Results II: Whole blood samples from 321 equids in The Gambia were processed under field conditions. There was weak agreement between LWB and TBR-PCR (Cohen’s kappa 0.34, 95% CI 0.19–0.49) but excellent agreement when testing CSF (100% agreement on 6 samples). Conclusions: Findings support that LAMP is comparable to PCR when used on CSF samples in the field, an important tool for clinical decision making. Results suggest repeatability is low in animals with low parasitaemia. Negative samples should be interpreted in the context of clinical presentation

Risk factors for lameness elimination in British endurance riding

Background: Horse welfare is a priority in the equine sport of endurance riding. Identification and reduction of risk factors associated with elimination and lameness have been the focus of research to date, however, this has centred on international competition. National federations recognise there is a need to consider risk factors for elimination at a more local level. Objectives: Determine current risk factors associated with horse eliminations, specifically lameness eliminations within British endurance. Study design: Retrospective cohort study. Methods: Data were extracted from the Endurance GB database, for open and advanced horses, competing in rides >64 km in the 2017 and 2018 competitive seasons. Variables were analysed via univariable models which informed subsequent multivariable binary logistic regression modelling. Two models were completed: (A) horse eliminated vs. not eliminated and (B) horse lame vs. not lame. Results: One thousand seven hundred and forty-seven competitive starts were analysed; 542 horses were eliminated. Lameness accounted for 56.1% (n = 304) of eliminations. Multivariable analysis identified decreased odds of lameness in graded rides compared with race rides (adjusted odds ratio, OR 0.6; 95% confidence interval, CI 0.4–0.8). There were increased odds of elimination (OR 4.7, CI 3.5–6.5) and increased odds of lameness (OR 1.9, CI 1.2–3.06) when competing in FEI competitions of 2* and above, compared to rides run under national rules. Horses and riders who had not competed as a combination previously had increased odds of elimination (OR 2.2, CI 1.5–3.02). Main limitations: Variables which can influence performance such as speed, environmental and topographical conditions were not recorded in the data set. Only two seasons of data were analysed. Conclusions: Competitive history of horses, including the number of previous starts, previous eliminations and the category of ride entered are significant in establishing the likelihood of elimination and more specifically lameness elimination in British national endurance

Comparison of loop-mediated isothermal amplification (LAMP) and PCR for the diagnosis of infection with Trypanosoma brucei spp. in equids in The Gambia.

Introduction: Infection of equids with Trypanosoma brucei (T. brucei) ssp. is of socioeconomic importance across sub-Saharan Africa as the disease often progresses to cause fatal meningoencephalitis. Loop-mediated isothermal amplification (LAMP) has been developed as a cost-effective molecular diagnostic test and is potentially applicable for use in field-based laboratories. Part I: Threshold levels for T. brucei ssp. detection by LAMP were determined using whole equine blood specimens spiked with known concentrations of parasites. Results were compared to OIE antemortem gold standard of T. brucei-PCR (TBR-PCR). Results I: Threshold for detection of T. brucei ssp. on extracted DNA from whole blood was 1 parasite/ml blood for LAMP and TBR-PCR, and there was excellent agreement (14/15) between tests at high (1 x 103/ml) concentrations of parasites. Detection threshold was 100 parasites/ml using LAMP on whole blood (LWB). Threshold for LWB improved to 10 parasites/ml with detergent included. Performance was excellent for LAMP at high (1 x 103/ml) concentrations of parasites (15/15, 100%) but was variable at lower concentrations. Agreement between tests was weak to moderate, with the highest for TBR-PCR and LAMP on DNA extracted from whole blood (Cohen’s kappa 0.95, 95% CI 0.64–1.00). Part II: A prospective cross-sectional study of working equids meeting clinical criteria for trypanosomiasis was undertaken in The Gambia. LAMP was evaluated against subsequent TBR-PCR. Results II: Whole blood samples from 321 equids in The Gambia were processed under field conditions. There was weak agreement between LWB and TBR-PCR (Cohen’s kappa 0.34, 95% CI 0.19–0.49) but excellent agreement when testing CSF (100% agreement on 6 samples). Conclusions: Findings support that LAMP is comparable to PCR when used on CSF samples in the field, an important tool for clinical decision making. Results suggest repeatability is low in animals with low parasitaemia. Negative samples should be interpreted in the context of clinical presentation

Clinical application of a scale to assess genomic healthcare empowerment (GEmS): Process and illustrative case examples

The Genome Empowerment Scale (GEmS), developed as a research tool, assesses perspectives of parents of children with undiagnosed disorders about to undergo exome or genome sequencing related to the process of empowerment. We defined genomic healthcare empowerment as follows: perceived ability to understand and seek new information related to the genomic sequencing, manage emotions related to the diagnostic process and outcomes, and utilize genomic sequencing information to the betterment of the individual/child and family. The GEmS consists of four scales, two are primarily emotion-focused (Meaning of a Diagnosis, and Emotional Management of the Process) and two are action-oriented (Seeking Information and Support, and Implications and Planning). The purpose of this research was to provide a strategy for interpreting results from the GEmS and present illustrative cases. These illustrations should serve to facilitate use of the GEmS in the clinical and research arena, particularly with respect to guiding genetic counseling processes for parents of children with undiagnosed conditions

A novel DPH5-related diphthamide-deficiency syndrome causing embryonic lethality or profound neurodevelopmental disorder

PurposeDiphthamide is a post-translationally modified histidine essential for messenger RNA translation and ribosomal protein synthesis. We present evidence for DPH5 as a novel cause of embryonic lethality and profound neurodevelopmental delays (NDDs).MethodsMolecular testing was performed using exome or genome sequencing. A targeted Dph5 knockin mouse (C57BL/6Ncrl-Dph5em1Mbp/Mmucd) was created for a DPH5 p.His260Arg homozygous variant identified in 1 family. Adenosine diphosphate-ribosylation assays in DPH5-knockout human and yeast cells and in silico modeling were performed for the identified DPH5 potential pathogenic variants.ResultsDPH5 variants p.His260Arg (homozygous), p.Asn110Ser and p.Arg207Ter (heterozygous), and p.Asn174LysfsTer10 (homozygous) were identified in 3 unrelated families with distinct overlapping craniofacial features, profound NDDs, multisystem abnormalities, and miscarriages. Dph5 p.His260Arg homozygous knockin was embryonically lethal with only 1 subviable mouse exhibiting impaired growth, craniofacial dysmorphology, and multisystem dysfunction recapitulating the human phenotype. Adenosine diphosphate-ribosylation assays showed absent to decreased function in DPH5-knockout human and yeast cells. In silico modeling of the variants showed altered DPH5 structure and disruption of its interaction with eEF2.ConclusionWe provide strong clinical, biochemical, and functional evidence for DPH5 as a novel cause of embryonic lethality or profound NDDs with multisystem involvement and expand diphthamide-deficiency syndromes and ribosomopathies