James B. Macelwane Award: Citation and Acceptance of Robert Keith O'Nions

I have the pleasure to introduce Robert Keith O'Nions, a young man of 34, for the Macelwane Award, not because I have had anything to do with his education and research, but because I was a member of the committee this year, and we both originate from the same country. Keith O'Nions earned his B.Sc. from the University of Nottingham in 1966, traveled to Alberta for a Ph.D. in 1969, became a Postdoctoral Fellow in Oslo during 1970, joined the faculty at Oxford from 1971–1975, and moved to his present home at Columbia University in 1975. When the time came to find a citationist [sic] for him it turned out that his colleagues at Lamont-Doherty, who were the obvious choices, were all at sea—and I admit that this is how I feel when I read some of Keith's papers. In a sense, this makes me well-suited for this introduction, because I cannot spend time explaining his research to you. Instead, I will read to you a couple of paragraphs from his nomination for the award, written by an anonymous friend

Attention-deficit hyperactivity disorder diagnoses and prescriptions in UK primary care, 2000–2018: population-based cohort study

Background Rates of diagnosed attention-deficit hyperactivity disorder (ADHD) may be increasing in the UK. Aims Estimate incidence and prevalence of ADHD diagnoses and ADHD prescriptions in UK adults and children in primary care. Method We conducted a cohort study using IQVIA Medical Research Data, a UK primary care database. Rates of ADHD diagnoses and ADHD prescriptions were calculated between 2000 and 2018 for individuals aged 3–99 years, analysed by age, gender, social deprivation status and calendar year. Results Of 7 655 931 individuals, 35 877 (0.5%) had ADHD diagnoses; 18 518 (0.2%) received ADHD medication prescriptions. Diagnoses and prescription rates were greater in men versus women, children versus adults, and deprivation status (nearly double in most deprived versus least deprived quintile). By 2018, the proportion of ADHD diagnoses was 255 per 10 000 (95% CI 247–263) in boys and 67.7 per 10 000 (95% CI 63.5–71.9) in girls; for adults, it was 74.3 per 10 000 (95% CI 72.3–76.2) in men and 20 per 10 000 (95%CI 19.0–21.0) in women. Corresponding figures for prescriptions were 156 per 10 000 (95% CI 150–163) in boys, 36.8 per 10 000 (95% CI 33.8–40.0) in girls, 13.3 per 10 000 (95% CI 12.5–14.1) in men and 4.5 per 10 000 (95% CI 4.1–5.0) in women. Except among 3- to 5-year-olds, the incidence and prevalence of ADHD diagnoses and prescriptions have increased from 2000 to 2018 in all age groups. The absolute increase was highest in children, but the relative increase was largest among adults (e.g. among men aged 18–29 years, approximately 20-fold and nearly 50-fold increases in diagnoses and prescriptions, respectively). Conclusions The incidence and prevalence of both ADHD diagnoses and medication are highest among children. Proportionally, rates increased most among adults during 2000–2018. ADHD diagnoses and prescriptions are associated with socioeconomic deprivation

p73 is over-expressed in vulval cancer principally as the Δ2 isoform

p73 was studied in squamous cancers and precursor lesions of the vulva. Over-expression of p73 occurred commonly in both human papillomavirus (HPV)-positive and -negative squamous cell cancers (SCC) and high-grade premalignant lesions. Whereas expression in normal vulval epithelium was detected only in the basal and supra-basal layers, expression in neoplastic epithelium increased with grade of neoplasia, being maximal at both protein and RNA levels in SCC. p73 Δ2 was the principal over-expressed isoform in the majority of cases of vulval SCC and often the sole form expressed in SCC. Over-expression of p73 was associated with expression of HPV-encoded E7 or with hypermethylation or mutation of p16INK4a in HPV-negative cases. There was a close correlation between expression of p73 and p14ARF in cancers with loss of p53 function. The frequent over-expression of p73 Δ2 in neoplastic but not normal vulval epithelium, and its co-ordinate deregulation with other E2F-1 responsive genes suggests a role in the oncogenic process. © 2001 Cancer Research Campaign  http://www.bjcancer.co

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

Scoping the future law and social justice - listening & hearing from the frontline: final report

'Scoping the Future Law and Social Justice – Listening & Hearing from the Frontline' ran for eight months from November 2021 until June 2022. The project aimed to identify research priorities for the AHRC in the area of law and social justice, a broad field of study with diverse points of focus. It explores the role that the law and legal institutions play in addressing contemporary social challenges such as those associated with gender, the COVID-19 pandemic, modern slavery, hate crime, inequality, the digital revolution, capitalism, and climate change to achieve a more just society, particularly around meeting the needs and safeguarding the rights of excluded, vulnerable and marginalised communities. In considering the subthemes identified by the AHRC (governance, citizenship & representation, transitional justice, and cultures of exclusion), we note that many of the current debates in these fields are underpinned by the notion of accountability. The project was designed around four workstreams (WS), which were designed to align with the AHRC and broader UKRI priorities. An interdisciplinary team at Nottingham Trent University undertook a comprehensive theoretical and empirical inquiry, informed by participatory action research, to formulate thematic and format-based recommendations for the AHRC. The research was co-designed with our research partners whom we refer to as ‘trusted intermediaries’ (TIs). Feedback and guidance were received from the Advisory Group (AG), represented by members of academia and the public whose work is broadly related to social justice issues. Six meetings with the AG, either collectively or individually were held, and their feedback has been indispensable for sharpening our project design and reflecting on progress. The team adopted a mixed-methods approach, combining a literature (scoping) review as well as qualitative data collection and analysis. Through different stages of the project, we have developed three templates to enable consistent collation of data across the research team. The first template sought to elicit the gaps in the existing literature. The second reflected on the data collected through individual interviews or focus groups. The third triangulated the literature, transcripts from interviews, and transcript and field notes analysis against five benchmarks which had been identified at the beginning of the project in consultation with our TIs. Overall, we conducted 29 partners and TI semi-structured interviews, and six interviews and three focus groups with service-users. Analysis of this data led to findings and team discussions. A first draft of the report was presented at a Roundtable for feedback from TIs and the government officials present. High quality research in the field of social justice, broadly defined, in the area of social justice is complex and multi-layered. This report recommends that future research in the field priorities stakeholder engagement that enables ongoing and respectful participatory research models involving the active co-design and collaboration of research partners. This should ensure that the nature of challenges in the field are properly understood, rather than based on assumptions contained in much of the established literature that may be outdated or may not be evidenced through the lived experiences of beneficiaries. While the research was commissioned by the AHRC, there are clear overlaps with the remit of the ESRC. Causes of social injustice (as the data and access to justice literature reflect) are complex and multi-layered, and key issues often intersect, compound, and are often structural in nature. Accordingly, academic ‘silos’ can be unhelpful in seeking to provide impactful and effective solutions to social injustice. This project has revealed fundamental inequities in policy and administrative settings that exacerbate exclusion. This report recommends that future research should prioritise interdisciplinary and participatory approaches which adopt shared language which cuts across disciplinary boundaries and is accessible to frontline service providers and end-users. While the research team for this project drew from expertise across different fields of law, politics and social psychology, we appreciate that future cross-disciplinary research might usefully draw upon the wider range of subject areas falling within the AHRC’s remit, including (but not limited to) to history, archaeology, anthropology, philosophy, languages, literature and the creative arts. This conclusion is based on our finding that creative pursuits can potentially play a useful role in reducing community isolation, build confidence, improve public trust and civic participation. The importance of interdisciplinary and cross-/multidisciplinary practise is also an area emerging as a way to improve responsiveness. This was noted by the REF2021 panel to be a point of strength and vibrancy in the current research landscape. The research findings also highlight the importance of using non-technical and accessible language and non- judgemental ways of working in order to gain buy-in from frontline service-providers, including groups who represent the interests of socially excluded communities. Such an approach would help to combat research fatigue and the sense of ‘being used but not included’ which had been flagged by a number of our TIs in relation to their involvement previous academic research projects. It is well established that austerity and competition for limited resources has had a major impact upon this sector. The sense of exhaustion and distrust should be acknowledged in in formulating future research strategies. While our own approach to this project can be characterised as iterative, reflective and responsive so as to enable a sense of ‘buy-in’ among our TIs, this has clearly not been the case in many previous research exercises. The allocation of future research funding should bear in mind the importance of co-design and collaboration to ensure that such funding represents value for money and that the nature of any findings are practical, relevant and evidence-based. These recommendations are in line with the REF panel’s observation that ‘the strongest submissions included Impact at all Points of the Research strategy and provided support, training and resources to develop External partnerships and relationships,’ further noting the ‘importance of outward focussing research with the outside organisation as ‘of vital importance to social progress and development. Our recommendations for the AHRC focus is on the general characteristics of the support needed, specific recommendations for next steps, aims, type, scale, timelines, justification of support needed as well as partners and their roles. 1. The AHRC would benefit from funding mid to long term “Engagement Research”: with local communities, NGOs (including Foodbanks, Legal Advice Centres, Domestic Abuse services with modest additional resources so as not to deflect from service delivery on the front line), local government, policy makers, corporations, legal practitioners etc. We have identified four themes for Engagement Research (trust, accountability, vulnerability, citizen’s rights) and 10 topics. 2. The AHRC should fund Fellowships that utilise opportunities to work on internship/externship models to partner with third sector agencies so that on-the ground practical realities can shape and support empirical, comparative, theoretical and doctrinal research to address current global and domestic challenges. These areas of study are key to address particular challenges for which researchers may find it difficult to secure funding from other sources due to the nature of their discipline and research. These fellowships may follow three different routes: AHRC Scholarship Fellowships, AHRC Interdisciplinary Fellowships, and AHRC Engagement Fellowships. We have identified six themes to engage with for AHRC. 3. AHRC should fund an independently evaluated pilot Digital Hub for police, which serves an important role in supplementing community policing by building and retaining useful shared information. Project design is in line with equality, diversity, and inclusion (EDI) criteria – which were taken into consideration not only with respect to how we have formed our team and distributed the tasks, but also how we recruited and drew on the expertise of partners and participants within the project

Estimating life expectancy and years of life lost for autistic people in the UK: a matched cohort study

Background Previous research has shown that people who have been diagnosed autistic are more likely to die prematurely than the general population. However, statistics on premature mortality in autistic people have often been misinterpreted. In this study we aimed to estimate the life expectancy and years of life lost experienced by autistic people living in the UK. Methods We studied people in the IQVIA Medical Research Database with an autism diagnosis between January 1, 1989 and January 16, 2019. For each participant diagnosed autistic, we included ten comparison participants without an autism diagnosis, matched by age, sex, and primary care practice. We calculated age- and sex-standardised mortality ratios comparing people diagnosed autistic to the reference group. We used Poisson regression to estimate age-specific mortality rates, and life tables to estimate life expectancy at age 18 and years of life lost. We analysed the data separately by sex, and for people with and without a record of intellectual disability. We discuss the findings in the light of the prevalence of recorded diagnosis of autism in primary care compared to community estimates. Findings From a cohort of nearly 10 million people, we identified 17,130 participants diagnosed autistic without an intellectual disability (matched with 171,300 comparison participants), and 6450 participants diagnosed autistic with an intellectual disability (matched with 64,500 comparison participants). The apparent estimates indicated that people diagnosed with autism but not intellectual disability had 1.71 (95% CI: 1.39–2.11) times the mortality rate of people without these diagnoses. People diagnosed with autism and intellectual disability had 2.83 (95% CI: 2.33–3.43) times the mortality rate of people without these diagnoses. Likewise, the apparent reduction in life expectancy for people diagnosed with autism but not intellectual disability was 6.14 years (95% CI: 2.84–9.07) for men and 6.45 years (95% CI: 1.37–11.58 years) for women. The apparent reduction in life expectancy for people diagnosed with autism and intellectual disability was 7.28 years (95% CI: 3.78–10.27) for men and 14.59 years (95% CI: 9.45–19.02 years) for women. However, these findings are likely to be subject to exposure misclassification biases: very few autistic adults and older-adults have been diagnosed, meaning that we could only study a fraction of the total autistic population. Those who have been diagnosed may well be those with greater support needs and more co-occurring health conditions than autistic people on average. Interpretation The findings indicate that there is a group of autistic people who experience premature mortality, which is of significant concern. There is an urgent need for investigation into the reasons behind this. However, our estimates suggest that the widely reported statistic that autistic people live 16-years less on average is likely incorrect. Nine out of 10 autistic people may have been undiagnosed across the time-period studied. Hence, the results of our study do not generalise to all autistic people. Diagnosed autistic adults, and particularly older adults, are likely those with greater-than-average support needs. Therefore, we may have over-estimated the reduction in life expectancy experienced by autistic people on average. The larger reduction in life expectancy for women diagnosed with autism and intellectual disability vs. men may in part reflect disproportionate underdiagnosis of autism and/or intellectual disability in women