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This thesis analyses whether attempts to reimagine the nation in plural terms can be successful in altering individuals’ conceptualisations of national identity and belonging. Drawing on theories of identity maintenance and ontological security (Giddens 1991), identity as performance (Butler, 1990; Goffman, 1959) and Mason’s (2013) concept of ‘cosmopolitan museology’, it questions the degree to which individuals are willing or able to accept plural representations of national identity increasingly seen in European museums such as the National Museum of Scotland. Such interpretative approaches attempt to deconstruct homogenous discourses of nationhood while encouraging individuals to develop a reflexive sense of self. This thesis argues that further research is needed into the way in which heritage is produced and negotiated in everyday social environments beyond the museum in order to understand what—if any— impact museums may have in producing ‘inclusive’ definitions of national identity. These issues are examined in Scotland, a devolved nation in the UK. The thesis critically analyses how young people aged between 13-17 years old from 5 schools in Glasgow, Edinburgh, Barra and the Scottish Borders utilised and negotiated concepts of ‘heritage’, ‘place’, ‘national identity’ and ‘diversity’ in narratives of belonging and exclusion. 73 young people participated in the research, which was conducted using focus groups and semi-structured interviews. The analysis also draws upon insights gained from teachers and heritage professionals. The research found that the majority of participants adopted positions that reinforced their existing sense of self, rather than alter their definitions of nationhood. While many participants were comfortable with the language of ‘diversity’, they frequently struggled to express themselves when applying these principles to everyday life. The findings indicate that museums could make a positive contribution to public debates by enabling individuals to articulate ideas of diversity while avoiding the essentialisation of difference.

BackgroundRisk factors for severe COVID-19 include older age, male sex, obesity, black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain.MethodsWe undertook a prospective, population-based cohort study (COVIDENCE UK) from 1 May 2020 to 5 February 2021. Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted ORs (aORs) for associations between potential risk factors and odds of COVID-19.ResultsWe recorded 446 incident cases of COVID-19 in 15 227 participants (2.9%). Increased odds of developing COVID-19 were independently associated with Asian/Asian British versus white ethnicity (aOR 2.28, 95% CI 1.33 to 3.91), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11 to 1.43), any versus no visits to/from other households in previous week (aOR 1.31, 1.06 to 1.62), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.02 to 1.09), frontline occupation excluding health/social care versus no frontline occupation (aOR 1.49, 1.12 to 1.98) and raised body mass index (BMI) (aOR 1.50 (1.19 to 1.89) for BMI 25.0–30.0 kg/m2 and 1.39 (1.06 to 1.84) for BMI >30.0 kg/m2 versus BMI <25.0 kg/m2). Atopic disease was independently associated with decreased odds (aOR 0.75, 0.59 to 0.97). No independent associations were seen for age, sex, other medical conditions, diet or micronutrient supplement use.ConclusionsAfter rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased odds of developing COVID-19, while atopic disease was associated with decreased odds.Trial registration numberClinicalTrials.gov Registry (NCT04330599).

ObjectivesCases of sporadic vestibular schwannoma (sVS) have a low rate of association with germline pathogenic variants. However, some individuals with sVS can represent undetected cases of neurofibromatosis type 2 (NF2) or schwannomatosis. Earlier identification of patients with these syndromes can facilitate more accurate familial risk prediction and prognosis.MethodsCases of sVS were ascertained from a local register at the Manchester Centre for Genomic Medicine. Genetic analysis was conducted in NF2 on blood samples for all patients, and tumour DNA samples when available. LZTR1 and SMARCB1 screening was also performed in patient subgroups.ResultsAge at genetic testing for vestibular schwannoma (VS) presentation was younger in comparison with previous literature, a bias resulting from updated genetic testing recommendations. Mosaic or constitutional germline NF2 variants were confirmed in 2% of patients. Pathogenic germline variants in LZTR1 were found in 3% of all tested patients, with a higher rate of 5% in patients <30 years. No pathogenic SMARCB1 variants were identified within the cohort. Considering all individuals who received tumour DNA analysis, 69% of patients were found to possess two somatic pathogenic NF2 variants, including those with germline LZTR1 pathogenic variants.ConclusionsUndiagnosed schwannoma predisposition may account for a significant minority of apparently sVS cases, especially at lower presentation ages. Loss of NF2 function is a common event in VS tumours and may represent a targetable common pathway in VS tumourigenesis. These data also support the multi-hit mechanism of LZTR1-associated VS tumourigenesis.

Individuals who have ocular features of albinism and skin pigmentation in keeping with their familial background present a considerable diagnostic challenge. Timely diagnosis through genomic testing can help avert diagnostic odysseys and facilitates accurate genetic counselling and tailored specialist management. Here, we report the clinical and gene panel testing findings in 12 children with presumed ocular albinism. A definitive molecular diagnosis was made in 8/12 probands (67%) and a possible molecular diagnosis was identified in a further 3/12 probands (25%). TYR was the most commonly mutated gene in this cohort (75% of patients, 9/12). A disease-causing TYR haplotype comprised of two common, functional polymorphisms, TYR c.[575 C > A;1205 G > A] p.[(Ser192Tyr);(Arg402Gln)], was found to be particularly prevalent. One participant had GPR143 -associated X-linked ocular albinism and another proband had biallelic variants in SLC38A8 , a glutamine transporter gene associated with foveal hypoplasia and optic nerve misrouting without pigmentation defects. Intriguingly, 2/12 individuals had a single, rare, likely pathogenic variant in each of TYR and OCA2 – a significant enrichment compared to a control cohort of 4046 individuals from the 100,000 genomes project pilot dataset. Overall, our findings highlight that panel-based genetic testing is a clinically useful test with a high diagnostic yield in children with partial/ocular albinism.

Public health measures implemented during the COVID-19 pandemic had widespread effects on population behaviors, transmission of infectious diseases, and exposures to environmental pollutants. This provided an opportunity to study how these factors potentially influenced the incidence of Kawasaki disease (KD), a self-limited pediatric vasculitis of unknown etiology. To examine the change in KD incidence across the United States and evaluate whether public health measures affected the prevalence of KD. This multicenter cohort study included consecutive, unselected patients with KD who were diagnosed between January 1, 2018, and December 31, 2020 (multicenter cohort with 28 pediatric centers), and a detailed analysis of patients with KD who were diagnosed between January 1, 2002, and November 15, 2021 (Rady Children's Hospital San Diego [RCHSD]). For the multicenter cohort, the date of fever onset for each patient with KD was collected. For RCHSD, detailed demographic and clinical data as well as publicly available, anonymized mobile phone data and median household income by census block group were collected. The study hypothesis was that public health measures undertaken during the pandemic would reduce exposure to the airborne trigger(s) of KD and that communities with high shelter-in-place compliance would experience the greatest decrease in KD incidence. A total of 2461 KD cases were included in the multicenter study (2018: 894; 2019: 905; 2020: 646), and 1461 cases (median [IQR] age, 2.8 years [1.4-4.9 years]; 900 [61.6%] males; 220 [15.1%] Asian, 512 [35.0%] Hispanic, and 338 [23.1%] White children) from RCHSD between 2002 and 2021 were also included. The 28.2% decline in KD cases nationally during 2020 (646 cases) compared with 2018 (894 cases) and 2019 (905 cases) was uneven across the United States. For RCHSD, there was a disproportionate decline in KD cases in 2020 to 2021 compared with the mean (SD) number of cases in earlier years for children aged 1 to 5 years (22 vs 44.9 [9.9]; P = .02), male children (21 vs 47.6 [10.0]; P = .01), and Asian children (4 vs 11.8 [4.4]; P = .046). Mobility data did not suggest that shelter-in-place measures were associated with the number of KD cases. Clinical features including strawberry tongue, enlarged cervical lymph node, and subacute periungual desquamation were decreased during 2020 compared with the baseline period (strawberry tongue: 39% vs 63%; P = .04; enlarged lymph node: 21% vs 32%; P = .09; periungual desquamation: 47% vs 58%; P = .16). School closures, masking mandates, decreased ambient pollution, and decreased circulation of respiratory viruses all overlapped to different extents with the period of decreased KD cases. KD in San Diego rebounded in the spring of 2021, coincident with lifting of mask mandates. In this study of epidemiological and clinical features of KD during the COVID-19 pandemic in the United States, KD cases fell and remained low during the period of masking and school closure. Mobility data indicated that differential intensity of sheltering in place was not associated with KD incidence. These findings suggest that social behavior is associated with exposure to the agent(s) that trigger KD and are consistent with a respiratory portal of entry for the agent(s).

Recent data suggest the urinary tract hosts a microbial community of varying composition, even in the absence of infection. Culture-independent methodologies, such as next-generation sequencing of conserved ribosomal DNA sequences, provide an expansive look at these communities, identifying both common commensals and fastidious organisms. A fundamental challenge has been the isolation of DNA representative of the entire resident microbial community, including fungi. We evaluated multiple modifications of commonly-used DNA extraction procedures using standardized male and female urine samples, comparing resulting overall, fungal and bacterial DNA yields by quantitative PCR. After identifying protocol modifications that increased DNA yields (lyticase/lysozyme digestion, bead beating, boil/freeze cycles, proteinase K treatment, and carrier DNA use), all modifications were combined for systematic confirmation of optimal protocol conditions. This optimized protocol was tested against commercially available methodologies to compare overall and microbial DNA yields, community representation and diversity by next-generation sequencing (NGS). Overall and fungal-specific DNA yields from standardized urine samples demonstrated that microbial abundances differed significantly among the eight methods used. Methodologies that included multiple disruption steps, including enzymatic, mechanical, and thermal disruption and proteinase digestion, particularly in combination with small volume processing and pooling steps, provided more comprehensive representation of the range of bacterial and fungal species. Concentration of larger volume urine specimens at low speed centrifugation proved highly effective, increasing resulting DNA levels and providing greater microbial representation and diversity. Alterations in the methodology of urine storage, preparation, and DNA processing improve microbial community profiling using culture-independent sequencing methods. Our optimized protocol for DNA extraction from urine samples provided improved fungal community representation. Use of this technique resulted in equivalent representation of the bacterial populations as well, making this a useful technique for the concurrent evaluation of bacterial and fungal populations by NGS.

Introduction: It is anticipated that by 2030 the number of older people and people living with long term conditions will have significantly increased. At the same time, it is expected that there will be a shift to providing more health care in the community. Browning et al [1] using a prospective 16-year longitudinal study of 1000 older Australians described three ageing groups (i) ageing well (30%); initially ageing well then deteriorating (50%); consistently ageing poorly (20%). Understanding the predictors of services use in older people is important in planning and providing quality care. Predictors of general practice service use from a small community-based studies have included: lower age, fewer medical conditions, restful sleep, good nutrition, decreased stress, being a non-smoker and good social support [2]. Using our existing data linkage resource, the Central and Eastern Sydney Primary and Community Health Cohort/Resource (CES-P&CH), which includes questionnaire data, primary care records, prescribing information, hospital records, emergency department records, cancer registry, and vital statistics on over 30,000 participants in CES aged 45 years and over (over 250,000 in NSW for comparison) we identified the predictors of service use (including general practice, pharmaceuticals, emergency departments, hospitalisations) amongst people aged over 75 years. Methods: A record linkage study using 45 and Up Study questionnaire data, MBS claims, PBS claims, Emergency Department visits, hospitalisations and deaths was undertaken. Participant characteristics at baseline (2006-2009) included demographics, health behaviours, social capital, functional status, and health conditions. Service characteristics included type of service, length of stay, location. Predictive models were developed to examine the participant/service characteristics with higher/lower service use over time. Results and Discussion: We identified 6,067 participants who were aged over 75 years in CES at baseline. Of these 59.0% had seen a GP 8 times or more in 2008, 19.6% had seen a specialist 8 times or more, 26.7% had attended an ED at least once, and 44.2% had been hospitalised at least once. In 2014 rates of GP use, specialist use and hospital admissions remained the same however ED visits had increased by 5%. This paper will discuss the different predictive models that were developed to describe service use. This paper will also provide the results from the predictive models and how this information is being/can be used to better plan and provide quality care for older people in CES. Limitations and suggestions for future research: Because the research study used an existing record linkage resource we were limited to the participant and service characteristics that were available. This research study would benefit from the inclusion on non-admitted data such as outpatient, community services and aged care services. References: 1- Browning C, Enticott J, Thomas S and Kendig H. 2017. Trajectories of ageing well among older Australians: a 16-year longitudinal study. Ageing and Society. 2017; 1-22. 2 -Korten AE, Jacomb PA, Jiao Z, Christensen H, Jorm AF, Henderson AS, Rodgers B. Predictors of GP service use: a community survey of an elderly Australian sample. Aust N Z J Public Health. 1998; 22: 609-615.

Objective To describe the processes of establishing and running the Cancer Experiences Collaborative (CECo), and reflect upon the benefits and challenges of undertaking collaborative research in supportive and palliative care. Design A descriptive analysis of a 5-year research collaborative initiated in 2006. Setting Research groups at the Universities of Lancaster, Liverpool, Manchester, Nottingham and Southampton, England. Participants 26 UK organisations including the four largest hospices in England, hospital cancer centres, Help the Hospices (a national charity supporting independent hospices) and user representatives. Findings The aim of CECo was to enhance the value, quality and productivity of scientific research in supportive and palliative care, and to increase research capacity and improve the coordination of collaborative research. Three programmatic themes of research were established: (i) innovative approaches to complex symptoms, (ii) planning for the care of older adults towards the end of life and (iii) research methodology including narrative approaches. Four benefits and challenges are highlighted: strategic leadership and management structures for cross-institutional work, working in multidisciplinary groups and linking research with practice settings, capacity building, and user involvement. Conclusions The activities of CECo have resulted in significant benefits with an increase in good quality research studies that have led to the production of a significant number of peer-reviewed papers, and learning between academics, clinicians and users, which has contributed to raising the standards of supportive and palliative care research. However, the future of such research initiatives is fragile, with concerns about the sustainability of collaboration in the face of diminishing resources.