Characterisation of the MICE experiment

Muon beams of low emittance would deliver intense, well-characterised neutrino beams necessary to explicate the physics of flavour at a Neutrino Factory and for high-luminosity lepton-antilepton collisions at a multi- TeV muon collider. The International Muon Ionisation Cooling Experiment (MICE), based at the Rutherford Appleton Laboratory, aims to demonstrate ionisation cooling, the technique proposed to reduce the emittance of muon beams at such facilities. An ionisation cooling channel has been constructed. The muon beam traverses a low-Z absorber material, losing energy via ionisation. The phase space volume occupied by the beam is reduced, resulting in transverse cooling. This thesis presents two independent analyses accomplished through exploiting data obtained during the “Step IV” commissioning of MICE. Muons can decay within the cooling channel. The presence of electron contaminants within MICE will generate systematic uncertainties on the cooling measurement. The angular distribution of decay electrons is dependent upon the muon polarisation. It is, therefore, imperative to characterise the impact of depolariza- tion in the channel. Chapter 4 presents a unique measurement of the polarisation of the MICE muon beam at the downstream calorimeter. For an initially unpolarised muon beam a polarisation of: -0.021 ± 0.243 (stat.) ± 0.185 (sys.) ± 0.007 (depol.) ± 0.001 (det.) is obtained, appropriately identifying the polarisation of the beam at the point of decay, within acknowledged errors. MICE is devised to possess an on-axis magnetic field. It is paramount that misalignment in the cooling channel is characterised. Chapter 5 ascertains a measurement of the central Focus Coil’s transverse position using single particle transfer matrices. No misalignment of the Focus Coil’s magnetic axis, relative to the beam axis, is observed, within the limits of the analysis. This innovative technique can be employed by any multi-element accelerator system where particle co-ordinates are quantified upon entering and exiting a constituent magnet.Open Acces

A Third Space in Lewiston: Exploring the Feasibility of Trinity Commons

The practice of “community building” is a complex and intricate mission. For communities that are populated by people of significantly different life experiences, this task may be especially challenging. Intermingling between subcommunities, generations, people of varying income levels, etc may not occur and neighbors may not have the chance to meet and build relationships with each other. This is evidently a huge loss - forging meaningful relationships with the people we share bits of our lives with is an incredibly valuable and rewarding experience. Unfortunately, in the context of the busyness of our daily lives, we are often inhibited from pursuing community building in its many forms. One potential avenue to escaping this cycle of isolation from one’s community is to create a context where community building is not only possible, but easy, simple, and the default. But how can this context be created? As explored by sociologists, this sort of effortless community building can be facilitated by the creation of a Third Space - a location that is distinct from both home and work environments and which is characterized by open communication, mutual respect and trust, and a safe space for self-expression, relationship building, and skill development. These spaces have the potential to create genuine and lasting relationships between community members by providing an equalizing and accessible location to socialize. The city of Lewiston, Maine is a vibrant, diverse, and complex place in the heart of south-central Maine. Previously a mill town, the city is now home to around 36,500 people, nearly 11,000 of whom live in the densely populated Tree Street neighborhood in downtown Lewiston (John T. Gorman Foundation). The Tree Street neighborhood is populated by a wide array of people of all ages, nationalities, races, ethnicities, income levels, etc. Though there are many community based organizations that prioritize community building, the missing piece of the puzzle is a physical location where different groups within the community could participate in classes, activities, art shows, performances, etc together in a neutral, accessible, and equalizing space. Our community partner, Klara Tammany, envisioned such a space existing in the Trinity Church building. Together, our team worked with Klara to create goals. Our project was focused on three main pillars of research: 1) exploring the function of community spaces as Third Spaces, 2) investigating the financial and management structure of organizations similarly situated to their community as Trinity Commons would be, and 3) producing a comprehensive overview of the potential expenses and revenue of the space. Our ultimate goal was to generate an expense report of the space and determine the financial viability of the project

Analysis of the orientation of cholesterol in high-density lipoprotein nanodiscs using solid-state NMR

Cholesterol is an essential component of eukaryotic cellular membranes that regulates the order and phase behaviour of dynamic lipid bilayers. Although cholesterol performs many vital physiological roles, hypercholesterolaemia and the accumulation of cholesterol in atherosclerotic plaques can increase the risk of coronary heart disease morbidity. The risk is mitigated by the transportation of cholesterol from peripheral tissue to the liver by high-density lipoprotein (HDL), 6–20 nm-diameter particles of lipid bilayers constrained by an annular belt of the protein apolipoprotein A-I (apoA-I). Information on the dynamics and orientation of cholesterol in HDL is pertinent to the essential role of HDL in cholesterol cycling. This work investigates whether the molecular orientation of cholesterol in HDL differs from that in the unconstrained lipid bilayers of multilamellar vesicles (MLVs). Solid-state NMR (ssNMR) measurements of dynamically-averaged (13)C–(13)C and (13)C–(1)H dipolar couplings were used to determine the average orientation of triple (13)C-labelled cholesterol in palmitoyloleoylphosphatidylcholine (POPC) lipid bilayers in reconstituted HDL (rHDL) nanodiscs and in MLVs. Individual (13)C–(13)C dipolar couplings were measured from [2,3,4-(13)C(3)]cholesterol in a one-dimensional NMR experiment, by using a novel application of a method to excite double quantum coherence at rotational resonance. The measured dipolar couplings were compared with average values calculated from orientational distributions of cholesterol generated using a Gaussian probability density function. The data were consistent with small differences in the average orientation of cholesterol in rHDL and MLVs, which may reflect the effects of the constrained and unconstrained lipid bilayers in the two environments. The calculated distributions of cholesterol in rHDL and MLVs that were consistent with the NMR data also agreed well with orientational distributions extracted from previous molecular dynamics simulations of HDL nanodiscs and planar POPC bilayers

Towards digital citizenship: a digital literacy curriculum to support teachers in the classroom

The purpose of this qualitative research is to generate theory that attempts to investigate, explore and “expand knowledge” (Bickman, 1981) in digital literacy skills and the needs of primary school teachers in educational training and Continuous Professional Development (CPD). Using its findings, an intervention framework was developed to empower teachers to support primary school children in an ever-changing digital landscape. This study followed a Constructivist Grounded Theory (CGT) research method, focusing on generating a new theory through the exploration of pre-existing theoretical frameworks in relevant literature and the inductive analysis of the data gathered from Phases 2 (interviews) and 3 (interventions) of the research process. Finding no agreed definition for ‘digital literacy’ in any given context during Phase 1 of the study, the researcher explored different models of digital literacy to create a definition of the phrase in a primary education setting: Digital literacy in education involves using technology creatively and developing functional skills, through exploration and practice. It is the understanding of e-safety by critically questioning the use of technology and information and the risks involved. This involves critically conducting searches to find and select relevant information using digital tools. It involves the ability to communicate and collaborate effectively online and with this have knowledge and understanding of cultural, social, and ethical behaviours. The researcher theorised that digital literacy in education consists of six components: functional skills, e-safety, finding and selecting relevant information, communication and collaboration, cultural, social, and ethical understanding, and creativity. The curriculum objectives of each component were determined after three-rounds of interviews with thirty-three practising teachers from North-East England, where questions were asked to gain an understanding of their digital literacy training needs which would be addressed in the training course. Findings showed the impact of COVID-19 saw these needs changing because of more frequent exposure and experience with teaching using technology, resulting in the development of digital literacy skills. Without an agreed definition for digital literacy, the skillset which teachers require is often unknown. This study proposes that teachers are trained in a foundation of digital literacy skills, specified to a primary educational context. Teachers will learn the required skills to ensure transferability as technology changes and digitalised societies advance. The significance of this research is that it informs educators of an overview of the six components of digital literacy in an educational context and suggests that delivery of a framework which provides training for teachers in this area, which can be adapted to suit any audience. The researcher suggests it may be adapted for CPD training, a HE module or a topic for primary school children

Germline genetic variation and predicting immune checkpoint inhibitor induced toxicity

Immune checkpoint inhibitor (ICI) therapy has revolutionised the treatment of various cancer types. ICIs reinstate T-cell function to elicit an anti-cancer immune response. The resulting immune response can however have off-target effects which manifest as autoimmune type serious immune-related adverse events (irAE) in ~10–55% of patients treated. It is currently challenging to predict both who will experience irAEs and to what severity. Identification of patients at high risk of serious irAE would revolutionise patient care. While the pathogenesis driving irAE development is still unclear, host genetic factors are proposed to be key determinants of these events. This review presents current evidence supporting the role of the host genome in determining risk of irAE. We summarise the spectrum and timing of irAEs following treatment with ICIs and describe currently reported germline genetic variation associated with expression of immuno-modulatory factors within the cancer immunity cycle, development of autoimmune disease and irAE occurrence. We propose that germline genetic determinants of host immune function and autoimmune diseases could also explain risk of irAE development. We also endorse genome-wide association studies of patients being treated with ICIs to identify genetic variants that can be used in polygenic risk scores to predict risk of irAE

Meal Timing Regulates the Human Circadian System

Circadian rhythms, metabolism and nutrition are intimately linked [1, 2], although effects of meal timing on the human circadian system are poorly understood. We investigated the effect of a 5-hour delay in meals on markers of the human master clock and multiple peripheral circadian rhythms. Ten healthy young men undertook a 13-day laboratory protocol. Three meals (breakfast, lunch, dinner) were given at 5-hour intervals, beginning either 0.5 (early) or 5.5 (late) hours after wake. Participants were acclimated to early meals and then switched to late meals for 6 days. After each meal schedule, participants' circadian rhythms were measured in a 37-hour constant routine that removes sleep and environmental rhythms while replacing meals with hourly isocaloric snacks. Meal timing did not alter actigraphic sleep parameters before circadian rhythm measurement. In constant routines, meal timing did not affect rhythms of subjective hunger and sleepiness, master clock markers (plasma melatonin and cortisol), plasma triglycerides, or clock gene expression in whole blood. Following late meals, however, plasma glucose rhythms were delayed by 5.69 ± 1.29 hours (p < 0.001) and average glucose concentration decreased by 0.27 ± 0.05 mM (p < 0.001). In adipose tissue, PER2 mRNA rhythms were delayed by 0.97 ± 0.29 hours (p < 0.01), indicating that human molecular clocks may be regulated by feeding time and could underpin plasma glucose changes. Timed meals therefore play a role in synchronising peripheral circadian rhythms in humans, and may have particular relevance for patients with circadian rhythm disorders, shift workers, and transmeridian travellers

Drug orientations within statin-loaded lipoprotein nanoparticles by 19F solid-state NMR

NMR measurements of 19F chemical shift anisotropy and 1H-19F dipolar couplings provide unprecedented information on the molecular orientations of two fluorine-containing statin drugs within the heterogeneous environment of reconstituted high-density lipoprotein (rHDL) nanoparticles, a drug delivery system under clinical investigation

Patient-reported respiratory outcome measures in the recovery of adults hospitalised with COVID-19: A systematic review and meta-analysis

Background Acute COVID-19 clinical symptoms have been clearly documented, but long-term functional and symptomatic recovery from COVID -19 is less well described.Methods A systematic review and meta-analysis were conducted to describe patient-reported outcome measures (PROMs) in adults at least 8 weeks post hospital discharge for COVID-19. Comprehensive database searches in accordance with the PRISMA statement were carried out up till 31/05/2021. Data were narratively synthesized, and a series of meta-analyses were performed using the random-effects inverse variance method.Results From 49 studies, across 14 countries with between 2-12 months follow up, the most common persisting symptom reported was fatigue with meta-analysis finding 36.6% (95 % CI 27.6 to 46.6, n=14) reporting it at 2-4 months, decreasing slightly to 32.5% still reporting it at >4 months (95% CI 22.6 to 44.2, n=15). This was followed by dyspnoea. Modified MRC score (mMRC) ≥1 was reported in 48% (95% CI 30 to 37, n=5) at 2-4months reducing to 32% (95% CI 22 to 43, n=7) at 4 months. Quality of life (QOL) as assessed by the EQ-5D-5L VAS remained reduced at >4 months (73.6 95% CI 68.1 to 79.1, n=6). Hospitalisation with COVID-19 also resulted in persisting sick leave, change in scope of work, and continued use of primary and secondary healthcare.Conclusion The symptomatic and functional impact of COVID-19 continues to be felt by patients months after discharge from hospital. This widespread morbidity points towards a multi-disciplinary approach to aid functional recovery