Helical waves in Earth's outer core

This thesis addresses the generation and dispersion of wave packets in Earth's outer core. The waves of interest feed off the buoyancy field, and are supported by strong rotation and/or a large-scale magnetic field, two key features of the dynamics in Earth's core. We aim to better understand the role of wave packets in shaping the turbulent convection, the process of magnetic induction, and maintaining Earth's magnetic field. Our numerical experiments focus on the emission of wave packets from localised sources, on the small length-scales of the convection, which stirs the fluid iron. The fluid flow in Earth's outer core is characterised by a small Rossby number, the ratio of nonlinear inertia and the Coriolis acceleration. However, due to computational constraints, many geodynamo simulations lie in a regime where the convective structures have a moderate Rossby number. These simulations, that over-estimate the influence of nonlinear inertia, undergo an abrupt transition from a columnar flow structure with a strongly dipolar magnetic field, to a state of disorganised flow accompanied by a multipolar field. This transition is commonly termed the \emph{dipolar-multipolar} transition, and the collapse of the dipole occurs when the \emph{`local'} Rossby number \citep[as introduced by][]{christensen2006} is greater than $0.1$. Separately, in the rotating turbulence literature, there is preliminary evidence of a similarly sharp transition from a columnar flow structure to incoherent turbulence when the Rossby number is $Ro \sim 0.2-0.6$. We show, that when $Ro > Ro^{\text{crit}} \approx 0.4$, inertial wave packets are suppressed, and columnar flow structures break down. Furthermore, we highlight a relationship between the `local' Rossby number used to describe the dipolar-multipolar transition and our $Ro$, which places both transitions at approximately $Ro^{\text{crit}}$. Based on this evidence, we conjecture that the breakdown of columnar structures, followed by the dipole collapse, is caused by the suppression of inertial wave packets at the critical threshold. In the following series of simulations, we study the effects of an ambient magnetic field on the dispersion of inertial wave packets. In the presence of an large-scale field, inertial waves are modified into a spectrum of waves called \emph{magnetic-Coriolis} waves, which present in a variety of forms depending on the wave-frequency. We focus on the Earth-like regime of rapid rotation and a small Lehnert number, $Le$, the ratio of the Alfv\'en and inertial frequencies. Our simulations initiated with a single buoyant blob yield an excellent comparison to the diffusion-less analytical results of \cite{bardsley2016} at $Ro \rightarrow 0$ and $Le = 0.1$. We identify three wave-types, predicted by linear theory, based on the waves' group velocity, helicity characteristics, and magnetic to kinetic energy ratio. At Earth-like values of $Le$, we observe that magnetic-Coriolis wave packets distribute helicity in a way that is beneficial to planetary magnetic field generation. Furthermore, the emf induced by the wave packets is coherent for Earth-like values of $Le$, suggesting than an $\alpha$-effect associated with the waves has the potential to drive a \emph{helical wave dynamo} \citep{davidson2014}

Comprehensive protein profiling of synovial fluid in osteoarthritis following protein equalization

Objective The aim of the study was to characterise the protein complement of synovial fluid (SF) in health and osteoarthritis (OA) using liquid chromatography mass spectrometry (LC-MS/MS) following peptide-based depletion of high abundance proteins. Design SF was used from nine normal and nine OA Thoroughbred horses. Samples were analysed with LC-MS/MS using a NanoAcquity™ LC coupled to an LTQ Orbitrap Velos. In order to enrich the lower-abundance protein fractions protein equalisation was first undertaken using ProteoMiner™. Progenesis-QI™ LC-MS software was used for label-free quantification. In addition immunohistochemistry, western blotting and mRNA expression analysis was undertaken on selected joint tissues. Results The number of protein identifications was increased by 33% in the ProteoMiner™ treated SF compared to undepleted SF. A total of 764 proteins (462 with≥2 significant peptides) were identified in SF. A subset of 10 proteins were identified which were differentially expressed in OA SF. S100-A10, a calcium binding protein was upregulated in OA and validated with western blotting and immunohistochemistry. Several new OA specific peptide fragments (neopeptides) were identified. Conclusion The protein equalisation method compressed the dynamic range of the synovial proteins identifying the most comprehensive SF proteome to date. A number of proteins were identified for the first time in SF which may be involved in the pathogenesis of OA. We identified a distinct set of proteins and neopeptides that may act as potential biomarkers to distinguish between normal and OA joints. Keywords Synovial fluid; Equalization; Osteoarthritis; S100-A10; Neopeptid

Transcriptome‐Wide Analysis of Messenger RNA Decay in Normal and Osteoarthritic Human Articular Chondrocytes

Objective Messenger RNA (mRNA) decay rates control not only gene expression levels, but also responsiveness to altered transcriptional input. We undertook this study to examine transcriptome‐wide posttranscriptional regulation in both normal and osteoarthritic (OA) human articular chondrocytes. Methods Human articular chondrocytes were isolated from normal or OA tissue. Equine articular chondrocytes were isolated from young or old horses at a commercial abattoir. RNA decay was measured across the transcriptome in human cells by microarray analysis following an actinomycin D chase. Messenger RNA levels in samples were confirmed using quantitative reverse transcription–polymerase chain reaction. Results Examination of total mRNA expression levels demonstrated significant differences in the expression of transcripts between normal and OA chondrocytes. Interestingly, almost no difference was observed in total mRNA expression between chondrocytes from intact OA cartilage and those from fibrillated OA cartilage. Decay analysis revealed a set of rapidly turned over transcripts associated with transcriptional control and programmed cell death that were common to all chondrocytes and contained binding sites for abundant cartilage microRNAs. Many transcripts exhibited altered mRNA half‐lives in human OA chondrocytes compared to normal cells. Specific transcripts whose decay rates were altered were generally less stable in these pathologic cells. Examination of selected genes in chondrocytes from young and old healthy horses did not identify any change in mRNA turnover. Conclusion This is the first investigation into the “posttranscriptome” of the chondrocyte. It identifies a set of short‐lived chondrocyte mRNAs likely to be highly responsive to altered transcriptional input as well as mRNAs whose decay rates are affected in OA chondrocytes

Barriers and facilitators of physical activity in adolescents with intellectual disabilities: An analysis informed by the COM-B model

BACKGROUND: Adolescents with intellectual disabilities are insufficiently physically active. Where interventions have been developed and delivered, these have had limited effectiveness, and often lack a theoretical underpinning. AIM: Through application of the COM‐B model, our aim is to explore the factors influencing adolescent physical activity within schools. METHODS: A qualitative methodology, using focus groups with students who have mild/moderate intellectual disabilities, their parents'/carers' and teachers'. The COM‐B model provided the lens through which the data were collected and analysed. RESULTS: We identified of a range of individual, interpersonal, and environmental factors influencing physical activity, across all six COM‐B constructs, within the context of the ‘school‐system’. CONCLUSION: This is the first study to use the COM‐B model to explore school‐based physical activity behaviour, for adolescents with intellectual disabilities. Identification of such physical activity behavioural determinants can support the development of effective and sustainable interventions

‘Walk Buds’: A walking intervention to increase physical activity, physical fitness, and emotional wellbeing, in 9–13 year old children with intellectual disabilities. Results of a clustered randomised feasibility trial

BACKGROUND: Children with intellectual disability are less physically active and more sedentary than typically developing peers. To date no studies have tested the feasibility of a school-based walking intervention for children with Intellectual Disability.METHOD: A clustered randomised controlled trial (cRCT), with an embedded process evaluation, was used to test the feasibility of a school-based walking intervention. Eight schools (n = 161 pupils aged 9-13 years) were randomised into either an intervention arm or an 'exercise as usual' arm. Measures included physical activity, physical fitness and emotional wellbeing. Baseline and 3-month follow-up data were collected.RESULTS: The 'Walk Buds' intervention was found to be acceptable to teaching staff and pupils, with an uptake rate of the walking sessions offered of 84%.CONCLUSION: A number of challenges were experienced, relating to the COVID-19 pandemic, and difficulties collecting accelerometer data. Barriers, facilitators and required changes identified through the mixed methods process evaluation are discussed.</p

Biomechanical changes of the trunk and lower limb during walking in patients after total hip arthroplasty for osteoarthritis: A systematic review and meta-analysis

Protocol for systematic literature revie

Affective and perceptual responses during reduced-exertion high-intensity interval training (REHIT)

We have previously demonstrated that reduced-exertion high-intensity interval training (REHIT) is a genuinely time-efficient exercise strategy for improving cardiometabolic health. Here, we examined the affective and perceptual responses to REHIT. Eight young men and women (age 21 ± 1 y, BMI 24.9 ± 2.1 m/kg2, V̇O2max 39 ± 10 ml/kg/min) and 11 men with type 2 diabetes (T2D; age 52 ± 6 y, BMI 29.7 ± 3.1 m/kg2, V̇O2max 29 ± 5 ml/kg/min) took part in three-arm crossover trials with RPE and affective valence measured during, and enjoyment and exercise preferences measured following either: 1) REHIT (2 × 20-s sprints in a 10-min exercise session), 2) HIIT (10 × 1-min efforts) and 3) 30 min MICT. Furthermore, 19 young men and women (age 25 ± 6 y, BMI 24 ± 4 m/kg2, V̇O2max 34 ± 8 ml/kg/min) completed a 6-week REHIT intervention with affective valence during an acute REHIT session measured before and after training. Affect decreases (briefly) during REHIT, but recovers rapidly, and the decline is not significantly different when compared to MICT or HIIT in either healthy participants or T2D patients. Young sedentary participants reported similar levels of enjoyment for REHIT, MICT and HIIT, but 7 out of 8 had a preference for REHIT. Conversely, T2D patients tended to report lower levels of enjoyment with REHIT compared with MICT. The decrease in affective valence observed during an acute REHIT session was significantly attenuated following training. We conclude that affective and perceptual responses to REHIT are no more negative compared to those associated with MICT or HIIT, refuting claims that supramaximal sprint interval training protocols are associated with inherent negative responses

Digital peer-to-peer support programme for informal caregivers of people living with motor neuron disease:study protocol for a multi-centre parallel group, single-blinded (outcome assessor) randomised controlled superiority trial

Background: Peer support is effective in improving psychological well-being of family caregivers of people with conditions such as dementia, cancer, and brain injury. However, there are limited data on effective psychological interventions for family caregivers of people living with motor neurone disease. Our objective is to evaluate the efficacy of a virtual peer support programme for improving caregiver psychological wellbeing and caregiving related outcomes. Methods: We will conduct a multi-centre parallel group randomised controlled superiority trial. Using a multi-modal recruitment strategy, we will recruit informal caregivers from UK MND clinics, in-patient units, and hospices. We will randomise (1:1, stratified by gender) participants to either a 12-week virtual peer support programme or usual care comprising provision of online information resources publicly available via the MND Association website. Peer support programme elements will be delivered via a secure digital e-platform aTouchAway™ (Aetonix, Canada). Our target sample size is 160 (80 each arm). Our primary outcome is the Hospital Anxiety and Depression Scale (HADS) assessed at 12 weeks (primary endpoint). Secondary outcomes that will also be assessed at 12 weeks include the Zarit Burden Interview, Pearlin Mastery Scale, Personal Gain Scale, Positive Affect Scale, and the Brief COPE. Outcome assessors will be blinded to allocation. Tertiary outcomes include perceived usability (1 item 9-point Likert scale) and acceptability (semi-structured qualitative interviews) of the peer support programme. Intervention fidelity measures will comprise frequency, type (text, audio, video), and duration (audio and video) of peer support contact downloaded from the aTouchAway AWS server. We will use a mixed-effects linear model to test the effect of the intervention on the primary outcome. Secondary outcomes will be analysed using linear regression. We have ethical approval (21/NW/0269) from the North-West Research Ethics Committee, UK. Discussion: This single-blinded randomised controlled trial will determine the effect of a virtual peer support programme on caregiver psychological wellbeing and caregiver burden. This study will examine the impact of a virtual peer support intervention on quality-of-life measures in informal caregivers of individuals with MND living in the community. Trial registration: ClinicalTrials.gov:</p

Targeted Induction of Endoplasmic Reticulum Stress Induces Cartilage Pathology

Pathologies caused by mutations in extracellular matrix proteins are generally considered to result from the synthesis of extracellular matrices that are defective. Mutations in type X collagen cause metaphyseal chondrodysplasia type Schmid (MCDS), a disorder characterised by dwarfism and an expanded growth plate hypertrophic zone. We generated a knock-in mouse model of an MCDS–causing mutation (COL10A1 p.Asn617Lys) to investigate pathogenic mechanisms linking genotype and phenotype. Mice expressing the collagen X mutation had shortened limbs and an expanded hypertrophic zone. Chondrocytes in the hypertrophic zone exhibited endoplasmic reticulum (ER) stress and a robust unfolded protein response (UPR) due to intracellular retention of mutant protein. Hypertrophic chondrocyte differentiation and osteoclast recruitment were significantly reduced indicating that the hypertrophic zone was expanded due to a decreased rate of VEGF–mediated vascular invasion of the growth plate. To test directly the role of ER stress and UPR in generating the MCDS phenotype, we produced transgenic mouse lines that used the collagen X promoter to drive expression of an ER stress–inducing protein (the cog mutant of thyroglobulin) in hypertrophic chondrocytes. The hypertrophic chondrocytes in this mouse exhibited ER stress with a characteristic UPR response. In addition, the hypertrophic zone was expanded, gene expression patterns were disrupted, osteoclast recruitment to the vascular invasion front was reduced, and long bone growth decreased. Our data demonstrate that triggering ER stress per se in hypertrophic chondrocytes is sufficient to induce the essential features of the cartilage pathology associated with MCDS and confirm that ER stress is a central pathogenic factor in the disease mechanism. These findings support the contention that ER stress may play a direct role in the pathogenesis of many connective tissue disorders associated with the expression of mutant extracellular matrix proteins