A search for star-forming galaxies at high redshift

This thesis describes the first search for star formation in primeval galaxies (PGs) at redshifts z ≥ 7. Our method was to undertake deep near- infrared imaging in the J window (~ 1.0 - 1.5μm) using four narrowband filters of 2% FWHM. Over an area of sky of 3.0□¹, no emission line object was found to a sensitivity limit of ≈10⁻¹⁸ Wm⁻². Interpreting this limit in terms of a limit on Lya emission, it has been possible to place the first constraints on star formation at redshifts 7 ≤ z ≤ 9. The search is also sensitive to other emission lines at lower redshifts, of particular interest are the constraints placed on Hα emission. This line is a direct tracer of star formation (Kennicutt et al., 1987) and, at the wavelengths of the narrowband filters, it probes redshifts 0.5 ≤ z ≤ 0.9. Constraints on the star formation rate at these redshifts are of great interest in the interpretation of the excess of faint blue objects seen in number counts (Tyson 1988, Lilly et al. 1991, Metcalfe et al. 1991, Jones et al., 1991).By assuming that there is no evolution in the comoving number density of galaxies out to z = 9, and that the luminosity function of objects at these redshifts can be represented by a Schechter function, it is possible to use the limits of the IRCAM search to place constraints on the characteristic Lya luminosity L*(Lyα) of PGs. Two extremes for the bright phase Δtbright of each galaxy are considered. In Case 1, Δtbright spans the four narrowband filters (~10⁸ years). In Case 2, the bright period is much shorter, and the specific case of the Partridge & Peebles (1966) model is considered (Atbright = 3 x 10⁷ years). The 95% confidence limits for Case 1 models constrain L*(Lyα) to less than 1.6 x 10³⁷ W - 4.2 x 10³⁷ W, depending on the cosmological model. These limits are consistent with the Case 1 predictions for Lyα luminosity. For the model of Partridge & Peebles (Case 2), the predicted PG luminosity is L*(Lyα) = 2 x 10³⁸ W. Assuming that at least some galaxies are in their luminous phase in each filter then, for high values of H□, this luminosity is inconsistent with the IRCAM limits. For Ho = 75kms- 1Mpc -1, luminosities greater than r 1 x 10³⁸W are ruled out at the 95% confidence level. For low values of H₀ however, the predicted PG luminosity is consistent with the limits. Greater areal coverage would enable the models to be more severely constrained, particularly as the effects of dust would further weaken the constraints.Using the Hα limits it is possible to constrain star formation rates in the merging model of Broadhurst et al. (1992). Assuming a constant star formation rate over the redshift range 0.52 ≤ z ≤ 0.92 then, for their best fit model, characteristic star formation rates greater than 12 M⨀ yr⁻¹ (q₀ = 0.5, h₅₀ = 1.0) can be ruled out at the 95% confidence level. This constraint tightens for lower values of qo and for higher values of H₀. These are very powerful constraints, since the local star formation rate is typically 3 -10 M⨀ yr⁻¹ for normal spirals, rising to 20 M⨀ yr⁻¹ in the more active spiral galaxies. If galaxy formation follows a merging scenario to z = 0.9 then the galaxies at these redshifts cannot be forming stars at a rate any greater than that observed locally

Sermo apologeticus: the evolution and development of Christian expression in Latin up to AD 250 and its later reception.

This thesis spans several disciplinary boundaries, theology, classics and linguistics, in seeking to trace the early development of Christian writing in Latin and to examine the later reception of this topic. Most studies concerned with this subject have focussed on the period from the fourth century, examining the wealth of primary source material available, particularly by Augustine, Jerome and Ambrose. In the present study I have concentrated my research on the earlier period, from the end of the second to the middle of the third century, which encompasses the works of Tertullian, the earliest extant Christian writer in Latin, and his near contemporary, Cyprian, Bishop of Carthage, whose death in 258 forms the terminus ad quem of this thesis. In the first chapter I outline the position of Latin usage in the period under discussion, focussing particularly on North Africa, a region in which Latin formed the language of communication much earlier an in other parts of the Roman Empire. The second chapter considers, against this background, the gradual emergence of Christian expression in Latin and its relationship, to Greek. A major part of this second chapter is devoted to the examination of the reception of Early Christian Latin, particularly the first study from a linguistic point of view carried out by Monsignor Joseph Schrijnen and Christine Mohrmann at the Catholic University of Nijmegen in the early part of the twentieth century, in which they developed the Sondersprache hypothesis, the theory that early Christians developed their own form of Latin. The third and fourth chapters are devoted to the study of the two major writers of the period mentioned above, Tertullian and Cyprian. This early period of Latin Christian writing thus lays the foundation for the great flowering of Christian writing which would emerge in the fourth century

Lessons learnt from delivering the public and patient involvement forums within a younger onset dementia project

Including the ‘voices’ of people living with dementia in a meaningful way is pivotal in shaping local, national and international health and social dementia care research. The Alzheimer’s Society (United Kingdom) funded Angela Project (2016–19) was aimed at improving the diagnosis and post-diagnostic support for younger people living with dementia. From the outset, the Project Team ensured that the knowledge and expertise of people living with a younger onset dementia was integral to all decisions taken in respect to overall project design, implementation, and dissemination processes. This was achieved by establishing two project public and patient involvement (PPI) forums; a London PPI Forum and a Bradford-based local PPI Hub. This paper describes how the two groups were formed; the format of the meetings; and the key points learnt by the Project Team from involving people with dementia in all aspects of developing and delivering the Angela Project. Ultimately, the aim is to demonstrate to other researchers in the dementia field how the perspectives of those with a diagnosis can be included in research studies in an active and meaningful way

Young-onset dementia: scoping review of key pointers to diagnostic accuracy

Background Routine psychiatric assessments tailored to older patients are often insufficient to identify the complexity of presentation in younger patients with dementia. Significant overlap between psychiatric disorders and neurodegenerative disease means that high rates of prior incorrect psychiatric diagnosis are common. Long delays to diagnosis, misdiagnosis and lack of knowledge from professionals are key concerns. No specific practice guidelines exist for diagnosis of young onset dementia (YOD). Aim The review evaluates the current evidence about best practice in diagnosis to guide thorough assessment of the complex presentations of YOD with a view to upskilling professionals in the field. Method A comprehensive search of the literature adopting a scoping review methodology was conducted regarding essential elements of diagnosis in YOD, over and above those in current diagnostic criteria for disease subtypes. This methodology was chosen because research in this area is sparse and not amenable to a traditional systematic review. Results The quality of evidence identified is variable with the majority provided from expert opinion and evidence is lacking on some topics. Evidence appears weighted towards diagnosis in fronto-temporal dementia (FTD) and its subtypes and young onset Alzheimer’s disease (AD). Conclusion The literature demonstrates that a clinically rigorous and systematic approach is necessary in order to avoid mis- or under-diagnosis for younger people. The advent of new disease modifying treatments necessitates clinicians in the field to improve knowledge of new imaging techniques and genetics, with the goal of improving training and practice, and highlights the need for quality indicators and alignment of diagnostic procedures across clinical settings

Interleukin-10 inhibits osteoclastogenesis by reducing NFATc1 expression and preventing its translocation to the nucleus

BACKGROUND: IL-10 has a potent inhibitory effect on osteoclastogenesis. In vitro and in vivo studies confirm the importance of this cytokine in bone metabolism, for instance IL-10-deficient mice develop the hallmarks of osteoporosis. Although it is known that IL-10 directly inhibits osteoclastogenesis at an early stage, preventing differentiation of osteoclast progenitors to preosteoclasts, the precise mechanism of its action is not yet clear. Several major pathways regulate osteoclastogenesis, with key signalling genes such as p38, TRAF6, NF-κB and NFATc1 well established as playing vital roles. We have looked at gene expression in eleven of these genes using real-time quantitative PCR on RNA extracted from RANKL-treated RAW264.7 monocytes. RESULTS: There was no downregulation by IL-10 of DAP12, FcγRIIB, c-jun, RANK, TRAF6, p38, NF-κB, Gab2, Pim-1, or c-Fos at the mRNA level. However, we found that IL-10 significantly reduces RANKL-induced NFATc1 expression. NFATc1 is transcribed from two alternative promoters in Mus musculus and, interestingly, only the variant transcribed from promoter P1 and beginning with exon 1 was downregulated by IL-10 (isoform 1). In addition, immunofluorescence studies showed that IL-10 reduces NFATc1 levels in RANKL-treated precursors and suppresses nuclear translocation. The inhibitory effect of IL-10 on tartrate-resistant acid phosphatase-positive cell number and NFATc1 mRNA expression was reversed by the protein kinase C agonist phorbol myristate acetate, providing evidence that interleukin-10 disrupts NFATc1 activity through its effect on Ca(2+ )mobilisation. CONCLUSION: IL-10 acts directly on mononuclear precursors to inhibit NFATc1 expression and nuclear translocation, and we provide evidence that the mechanism may involve disruption of Ca(2+ )mobilisation. We detected downregulation only of the NFATc1 isoform 1 transcribed from promoter P1. This is the first report indicating that one of the ways in which IL-10 directly inhibits osteoclastogenesis is by suppressing NFATc1 activity

A hafted halberd excavated at Trecastell, Powys: from undercurrent to uptake – the emergence and contextualisation of halberds in Wales and North-west Europe

Excavations at Trecastell, Powys, south Wales, in 2007 yielded a copper halberd complete with its haft-grip. This has major implications for the mode of hafting halberds, but the discovery has also prompted a reconsideration of insular halberds in their north-west European context. Understanding the relationships between different types of halberd and different regional groups continues to be hampered by the dearth of good dating evidence, but the creation of better classifications for British and Irish weapons and new radiocarbon dates on two examples, one being Trecastell, have allowed a new developmental scheme to be advanced.The emergence of metal-headed halberds is considered more generally. While it is acknowledged that halberd-like implements pre-existed in other materials in some parts of Europe, it is argued that the appearance of metal-headed halberds depended on the transmission of a particular set of metallurgical and related skills. A new model for the vigorous uptake of halberds on a regional basis helps explain the patchiness and anachronism of halberd hotspots.The Trecastell halberd adds to one of the significant concentrations of the weapon type in Britain and prompts a more general review of the earliest metalwork from Wales and the Marches. For the Chalcolithic, halberds are instrumental in identifying a major contrast in depositional behaviour; this contrast dissolves at the beginning of the Early Bronze Age when a ‘new deposition ground’ is established. The former is attributed to the existence of a regional group across much of the region for whom the halberd served as a cultural icon, while the latter may relate to the demise of this enshrined value for the halberd.</jats:p

Reducing the within-patient variability of breathing for radiotherapy delivery in conscious, unsedated cancer patients using a mechanical ventilator

OBJECTIVE: Variability in the breathing pattern of patients with cancer during radiotherapy requires mitigation, including enlargement of the planned treatment field, treatment gating and breathing guidance interventions. Here, we provide the first demonstration of how easy it is to mechanically ventilate patients with breast cancer while fully conscious and without sedation, and we quantify the resulting reduction in the variability of breathing. METHODS: 15 patients were trained for mechanical ventilation. Breathing was measured and the left breast anteroposterior displacement was measured using an Osiris surface-image mapping system (Qados Ltd, Sandhurst, UK). RESULTS: Mechanical ventilation significantly reduced the within-breath variability of breathing frequency by 85% (p < 0.0001) and that of inflation volume by 29% (p < 0.006) when compared with their spontaneous breathing pattern. During mechanical ventilation, the mean amplitude of the left breast marker displacement was 5 ± 1 mm, the mean variability in its peak inflation position was 0.5 ± 0.1 mm and that in its trough inflation position was 0.4 ± 0.0 mm. Their mean drifts were not significantly different from 0 mm min(−1) (peak drift was −0.1 ± 0.2 mm min(−1) and trough drift was −0.3 ± 0.2 mm min(−1)). Patients had a normal resting mean systolic blood pressure (131 ± 5 mmHg) and mean heart rate [75 ± 2 beats per minute (bpm)] before mechanical ventilation. During mechanical ventilation, the mean blood pressure did not change significantly, mean heart rate fell by 2 bpm (p < 0.05) with pre-oxygenation and rose by only 4 bpm (p < 0.05) during pre-oxygenation with hypocapnia. No patients reported discomfort and all 15 patients were always willing to return to the laboratory on multiple occasions to continue the study. CONCLUSION: This simple technique for regularizing breathing may have important applications in radiotherapy. ADVANCES IN KNOWLEDGE: Variations in the breathing pattern introduce major problems in imaging and radiotherapy planning and delivery and are currently addressed to only a limited extent by asking patients to breathe to auditory or visual guidelines. We provide the first demonstration that a completely different technique, of using a mechanical ventilator to take over the patients' breathing for them, is easy for patients who are conscious and unsedated and reduces the within-patient variability of breathing. This technique has potential advantages in radiotherapy over currently used breathing guidance interventions because it does not require any active participation from or feedback to the patient and is therefore worthy of further clinical evaluation

Room to move: impacts of road-space reallocation

The Covid-19 pandemic and associated national lockdowns rapidly reduced personal mobility and led to a rethinking of travel behaviours, at least for the short-term. Whilst on-going uncertainty makes longer-term planning difficult, this project looks back to establish the impacts of the pandemic on two contrasting local authorities in the North of England: Lancashire and Sheffield. Through a three-wave longitudinal panel study, this project has examined changes in travel behaviour emerging from the pandemic, the role and effect of temporary road-space reallocation measures and begins to explore what the resulting longer-term impacts are