The contribution of proprioceptive acuity to upper limb motor performance in older and younger adults

As we get older there is an increase in the variability of upper limb movements which typically require greater reliance on online corrective mechanisms. However, the relative contribution of proprioceptive loss to the development of these impairments in the upper limb is not well understood. The work in this thesis aimed to address this by presenting a novel method of measuring upper limb proprioception using a 2D-robotic manipulandum with older and younger adults. We show that this task provides distinct measures from traditional methods, and that despite physically inactive older adults having larger systematic errors in judging limb position, this was not related to motor performance during rapid target reaching. Furthermore, there was also a null relationship with the extent of motor adaptation to novel field dynamics even when only proprioceptive information regarding the perturbation was available. We were unable to measure robust effects of ageing on proprioceptive acuity throughout the thesis, and suggest that the level of impairment may have been previously over-inflated due to task and population specific limitations as a result. Collectively, we found a limited role of proprioceptive loss in the presentation of age-related impairments in motor control

Muscular activation and corticospinal excitability adaptations to split crank cycling

Foot drop is a common motor impairment of the lower limb caused by Acquired Brain Injury (ABI) that can limit mobility and increase risk of falls. Split Crank (SC) cycling is proposed here as a novel paradigm to evoke functional neural plasticity and beneficial muscular adaptations to treat foot drop. Healthy participants were randomly assigned to SC or FC conditions for a 5 day intervention. Transcranial magnetic stimulation (TMS) evoked stimulus-response curves (SRCs) for tibialis anterior (TA) and muscle kinematic activation patterns for TA, soleus (SOL), biceps femoris (BF) and vastus lateralis (VL) during cycling were recorded before and after the first and last training sessions. SRCs revealed no beneficial TA corticospinal excitability adaptations to training but significant increases in duration of TA and BF activity were reported for TA and BF during SC cycling (p < .05). This occurred as an immediate response on initial exposure to the task. The strength of evidence for implementing SC cycling with ABI patients in the treatment of foot drop was weaker than hoped. However, increased duration of TA activation shows promise as beneficial for foot drop sufferers. Completion of the study provided new information on an unexplored exercise therapy and useful observations for facilitating clinical translation in the future

Cryptic Distant Relatives Are Common in Both Isolated and Cosmopolitan Genetic Samples

Although a few hundred single nucleotide polymorphisms (SNPs) suffice to infer close familial relationships, high density genome-wide SNP data make possible the inference of more distant relationships such as 2nd to 9th cousinships. In order to characterize the relationship between genetic similarity and degree of kinship given a timeframe of 100–300 years, we analyzed the sharing of DNA inferred to be identical by descent (IBD) in a subset of individuals from the 23andMe customer database (n = 22,757) and from the Human Genome Diversity Panel (HGDP-CEPH, n = 952). With data from 121 populations, we show that the average amount of DNA shared IBD in most ethnolinguistically-defined populations, for example Native American groups, Finns and Ashkenazi Jews, differs from continentally-defined populations by several orders of magnitude. Via extensive pedigree-based simulations, we determined bounds for predicted degrees of relationship given the amount of genomic IBD sharing in both endogamous and ‘unrelated’ population samples. Using these bounds as a guide, we detected tens of thousands of 2nd to 9th degree cousin pairs within a heterogenous set of 5,000 Europeans. The ubiquity of distant relatives, detected via IBD segments, in both ethnolinguistic populations and in large ‘unrelated’ populations samples has important implications for genetic genealogy, forensics and genotype/phenotype mapping studies

Proprioceptive loss and the perception, control and learning of arm movements in humans: evidence from sensory neuronopathy

© 2018 The Author(s) It is uncertain how vision and proprioception contribute to adaptation of voluntary arm movements. In normal participants, adaptation to imposed forces is possible with or without vision, suggesting that proprioception is sufficient; in participants with proprioceptive loss (PL), adaptation is possible with visual feedback, suggesting that proprioception is unnecessary. In experiment 1 adaptation to, and retention of, perturbing forces were evaluated in three chronically deafferented participants. They made rapid reaching movements to move a cursor toward a visual target, and a planar robot arm applied orthogonal velocity-dependent forces. Trial-by-trial error correction was observed in all participants. Such adaptation has been characterized with a dual-rate model: a fast process that learns quickly, but retains poorly and a slow process that learns slowly and retains well. Experiment 2 showed that the PL participants had large individual differences in learning and retention rates compared to normal controls. Experiment 3 tested participants’ perception of applied forces. With visual feedback, the PL participants could report the perturbation’s direction as well as controls; without visual feedback, thresholds were elevated. Experiment 4 showed, in healthy participants, that force direction could be estimated from head motion, at levels close to the no-vision threshold for the PL participants. Our results show that proprioceptive loss influences perception, motor control and adaptation but that proprioception from the moving limb is not essential for adaptation to, or detection of, force fields. The differences in learning and retention seen between the three deafferented participants suggest that they achieve these tasks in idiosyncratic ways after proprioceptive loss, possibly integrating visual and vestibular information with individual cognitive strategies

New East Manchester: urban renaissance or urban opportunism?

In this paper we ask how a shrinking city responds when faced with a perforated urban fabric. Drawing on Manchester’s response to its perforated eastern flank - and informed by a parallel study of Leipzig - we use the city’s current approach to critique urban regeneration policy in England. Urban renaissance holds out the promise of delivering more sustainable - that is more compact, more inclusive and more equitable - cities. However, the Manchester study demonstrated that the attempt to stem population loss from the city is at best fragile, despite a raft of policies now in place to support urban renaissance in England. It is argued here that Manchester like Leipzig is likely to face an ongoing battle to attract residents back from their suburban hinterlands. This is especially true of the family market that we identify as being an important element for long-term sustainable population growth in both cities. We use the case of New East Manchester to consider how discourses linked to urban renaissance – particularly those that link urbanism with greater densities - rule out some of the options available to Leipzig, namely, managing the long-term perforation of the city. We demonstrate that while Manchester is inevitably committed to the urban renaissance agenda, in practice New East Manchester demonstrates a far more pragmatic – but equally unavoidable – approach. This we attribute to the gap between renaissance and regeneration described by Amin et al (2000) who define the former as urbanism for the middle class and the latter as urbanism for the working class. While this opportunistic approach may ultimately succeed in producing development on the ground, it will not address the fundamental, and chronic, problem; the combination of push and pull that sees families relocating to suburban areas. Thus, if existing communities in East Manchester are to have their area buoyed up – or sustained - by incomers, and especially families, with greater levels of social capital and higher incomes urban policy in England will have to be challenged

Reconstructing Native American Population History

The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved1–5. One contentious issue is whether the settlement occurred via a single6–8 or multiple streams of migration from Siberia9–15. The pattern of dispersals within the Americas is also poorly understood. To address these questions at higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. We show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call “First American”. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan-speakers on both sides of the Panama Isthmus, who have ancestry from both North and South America

Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant