Complexity and diversity in the late iron age southern Levant: the investigation of 'Edomite' archaeology and scholarly discourse

This thesis aims to reassess the principal concepts used by archaeologists in their attempts to interpret the late Iron Age archaeology of southern Israel and Jordan. This study focuses in particular on the archaeological remains that have traditionally been associated with the 'Edomites' mentioned in the Old Testament. This reassessment involves examining two inter-related themes. The first is largely historiographical, the aim being to highlight the socio-political and intellectual contexts in which the study of the 'Edomites' became an important discourse. This is achieved by contextualising both the beginnings of south Levantine Iron Age archaeology as a whole and the archaeological investigation of the 'Edomites', as well as the study of the historical sources that mention Edom' and the 'Edomites'. The second theme concerns the material culture used by archaeologists to address questions regarding the 'Edomites', such as the areas they spread to, whether they spread by migration, invasion, or trade, and the nature of their kingdom and religion. Firstly, the theoretical underpinnings of these archaeological approaches is reassessed. Building on that, an analysis of what is traditionally interpreted as 'Edomite' pottery - material that has been commonly used to address the questions posed above - is presented. This analysis focuses on the ways in which this type of pottery was used, and where possible, the contexts in which it was deposited/found, thus highlighting how people in the past used it as part of specific social practices. The results demonstrate that the pattern of material culture usually thought to underpin traditional understandings of 'Edomite' archaeology is actually quite varied and that 'Edomite' ethnicity may not be the best explanation for such diversity. Following the critique of the discourse of 'Edomite' archaeology, a number of alternative ways in which the late Iron Age material culture of the southern Levant might be understood are suggested. These alternatives focus on theories of practice, appropriation, and foodways

Development of a redox-free mitsunobu reaction exploiting phosphine oxides as precursors to dioxyphosphoranes

The development of the first redox-free protocol for the Mitsunobu reaction is described. This has been achieved by exploiting triphenylphosphine oxide – the unwanted by-product in the conventional Mitsunobu reaction – as the precursor to the active P(V) coupling reagent. Multinuclear NMR studies are consistent with hydroxyl activation via an alkoxyphosphonium salt

Being a child with intellectual disabilities in hospital: The need for an individualised approach to care

BACKGROUND: There is limited qualitative research focussed specifically on what it is like for children and young people with intellectual disabilities coming into hospital, with much of the evidence-base being about those with Autism Spectrum Condition or adults with intellectual disabilities. AIM: To share rich detail of the emotional and physical impact on children and young people with intellectual disabilities of attending hospital, from their own and their parent's perspective. METHODS: Talking Mats interviews, sticker survey and photography with children and young people with intellectual disabilities, and in-depth interviews, hospital diaries and photography with their parents. RESULTS AND CONCLUSIONS: The multiple and compounding layers of complexity surrounding hospital care of children and young people with intellectual disabilities resulted in challenges associated with loss of familiarity and routine, undergoing procedures, managing sensory overload, managing pain and having a lack of safety awareness. An individualised approach to their care is needed

α-conotoxin GI triazole-peptidomimetics: potent and stable blockers of a human acetylcholine receptor

The potency and selectivity of conotoxin peptides for neuropathic receptors has made them attractive lead compounds in the development of new therapeutics. Specifically, α-conotoxin GI has been shown to be an unparalleled antagonist of the nicotinic acetylcholine receptor (nAChR). However, as with other peptidic leads, poor protease resistance and the redox instability of the conotoxin scaffold limit bioactivity. To counter this, we have employed the underutilised 1,5-disubstituted 1,2,3-triazole to act as a structural surrogate of the native disulfide bonds. Using an efficient, on-resin ruthenium azide-alkyne cycloaddition (RuAAC), each disulfide bond was replaced in turn and the biological activities quantified. One of the mimetic isomers exhibited a comparable activity to the native toxin, while the other showed no biological effect. The active mimetic isomer 11 was an order of magnitude more stable in plasma than the native GI. The NMR solution structure of the mimetic overlays extremely well with the structure for the native GI demonstrating that the triazole bridge is an exceptional surrogate for the disulfide bridge. Development of this potent and stable mimetic of GI leads us to believe that this strategy will yield many other new conotoxin-inspired probes and therapeutics

μ-conotoxin KIIIA peptidomimetics that block human voltage-gated sodium channels

Peptidomimetics designed to target voltage‐gated sodium channels have attracted significant attention as potential analgesics. However, voltage‐gated sodium channel (VGSC)‐blocking activity of these compounds has mainly been assessed using rat and/or mice homologs. In this study, we developed a novel series of conformationally constrained peptidomimetic analogues of the μ‐conotoxin KIIIA and assessed their activity against human VGSCs. Two of the mimetics block the currents of hNav1.4 and hNav1.6 channels. NMR derived structures of the mimetics provided excellent insight into the structural requirements for bioactivity. A lactam‐constrained analogue, previously reported to be active in mice, did not block the corresponding human VGSC. This work highlights important differences in VGSCs between species and validates the potential of peptidomimetics as human analgesics

Equal access to hospital care for children with learning disabilities and their families : a mixed-methods study

Background To our knowledge, there has yet to be a comprehensive review of how well hospital services are meeting the needs of children and young people (hereafter referred to as children) with learning disability and their families. The extent to which their experiences differ from those of parents of children without learning disability is not known. The views and experiences of children with learning disability are almost non-existent in the literature. Aims To identify the cross-organisational, organisational and individual factors in NHS hospitals that facilitate and prevent children with learning disability and their families receiving equal access to high-quality care and services, and to develop guidance for NHS trusts. Design A four-phase transformative, mixed-methods case study design comparing the experiences of children with and children without learning disability, their parents and health-care staff. Methods Phase 1 comprised interviews with senior managers (n = 65), content analysis of hospital documents and a staff survey (n = 2261) across 24 hospitals in England, including all specialist children’s hospitals. Phases 2–4 involved seven of these hospitals. Phase 2 involved (a) interviews and photography with children and their parents (n = 63), alongside a parent hospital diary and record of safety concerns; (c) hospital staff interviews (n = 98) and community staff survey (n = 429); and (d) retrospective mapping of hospital activity. During phase 3, children (n = 803) and parents (n = 812) completed satisfaction surveys. Phase 4 involved seeking consultation on the findings. Data analysis A model for mixed-methods data analysis and synthesis was used. Qualitative data were managed and analysed thematically, supported with NVivo (QSR International, Warrington, UK). Quantitative data were analysed using parametric and non-parametric descriptive statistics. Results Nationally, there is considerable uncertainty within hospitals and variation between hospitals in terms of the policies, systems and practices in place specifically for children with learning disability. Staff are struggling to individualise care and are being let down by an inadequate system. Attitudes and assumptions can have a lasting impact on parents and children. The findings serve as a useful guide to trusts about how best to meet the Learning Disability Improvement standards that have been set. Conclusions Safety issues and quality of care affect all children in acute hospitals and their parents, but the impact on children with learning disability and their parents is much greater. Individualising care is key. Our findings suggest that staff may need to undertake training and gain experience to build their skills and knowledge about children with learning disability generally, as well as generate knowledge about the individual child through proactively working in partnership with parents before their child’s admission. The findings also suggest that we may need to address the impact of children’s hospitalisation on parents’ health and well-being. Future work The greatest need is for the development and validation of an instrument for the assessment and management of risk in children with learning disability in hospital. Limitations We cannot say with certainty that the sites selected are representative of all services caring for children with learning disability. Study registration The study has been registered on the National Institute for Health and Care Research (NIHR) Clinical Research Network portfolio as 20461 (phase 1) and 31336 (phases 2–4). Funding This project was funded by the NIHR Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 13. See the NIHR Journals Library website for further project information

Reversible Induction of Phantom Auditory Sensations through Simulated Unilateral Hearing Loss

Tinnitus, a phantom auditory sensation, is associated with hearing loss in most cases, but it is unclear if hearing loss causes tinnitus. Phantom auditory sensations can be induced in normal hearing listeners when they experience severe auditory deprivation such as confinement in an anechoic chamber, which can be regarded as somewhat analogous to a profound bilateral hearing loss. As this condition is relatively uncommon among tinnitus patients, induction of phantom sounds by a lesser degree of auditory deprivation could advance our understanding of the mechanisms of tinnitus. In this study, we therefore investigated the reporting of phantom sounds after continuous use of an earplug. 18 healthy volunteers with normal hearing wore a silicone earplug continuously in one ear for 7 days. The attenuation provided by the earplugs simulated a mild high-frequency hearing loss, mean attenuation increased from <10 dB at 0.25 kHz to >30 dB at 3 and 4 kHz. 14 out of 18 participants reported phantom sounds during earplug use. 11 participants presented with stable phantom sounds on day 7 and underwent tinnitus spectrum characterization with the earplug still in place. The spectra showed that the phantom sounds were perceived predominantly as high-pitched, corresponding to the frequency range most affected by the earplug. In all cases, the auditory phantom disappeared when the earplug was removed, indicating a causal relation between auditory deprivation and phantom sounds. This relation matches the predictions of our computational model of tinnitus development, which proposes a possible mechanism by which a stabilization of neuronal activity through homeostatic plasticity in the central auditory system could lead to the development of a neuronal correlate of tinnitus when auditory nerve activity is reduced due to the earplug

An ASKAP search for a radio counterpart to the first high-significance neutron star-black hole merger LIGO/Virgo S190814bv

We present results from a search for a radio transient associated with the LIGO/Virgo source S190814bv, a likely neutron star–black hole (NSBH) merger, with the Australian Square Kilometre Array Pathfinder. We imaged a 30 deg² field at ΔT = 2, 9, and 33 days post-merger at a frequency of 944 MHz, comparing them to reference images from the Rapid ASKAP Continuum Survey observed 110 days prior to the event. Each epoch of our observations covers 89% of the LIGO/Virgo localization region. We conducted an untargeted search for radio transients in this field, resulting in 21 candidates. For one of these, AT2019osy, we performed multiwavelength follow-up and ultimately ruled out the association with S190814bv. All other candidates are likely unrelated variables, but we cannot conclusively rule them out. We discuss our results in the context of model predictions for radio emission from NSBH mergers and place constrains on the circum-merger density and inclination angle of the merger. This survey is simultaneously the first large-scale radio follow-up of an NSBH merger, and the most sensitive widefield radio transients search to-date

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy