We explore if there is potential to embed psychosocial well‐being impact in global challenges research where the primary aims are not mental health related. We are interested in the use of material practices to deliver impact through routine project activities of working with concrete things together. The UK Research and Innovation (UKRI) gateway to research was searched for information on Global Challenges Research Fund (GCRF) grants from 2015 to May 2020. Analysis shows that only 3 per cent of projects self‐categorise as engaging with mental health. Thirty‐six non‐mental health GCRF grants were purposefully sampled for diversity, and each was coded independently by two researchers for relevant information. Findings suggest that 50–70 per cent of non‐mental health GCRF projects already engage implicitly, but nonstrategically, with psychosocial well‐being impact; opportunities for psychosocial well‐being impact, from most to least frequent, are community mobilisation, community building, skills development, positive sense of self, positive emotions and sociocultural identity; the presence of material practice from most to least frequent is as follows: (i) interactions between or enactments upon people, (ii) written materials or images, and (iii) objects; when a material practice was present, it was usually considered usable as a focus to enhance psychosocial well‐being. Our study provides evidence that there are low hanging fruit opportunities to impact psychosocial well‐being across Sustainable Development Goals (SDGs) through routine project activities. Our World in Data at the University of Oxford reports that, in 2017, 1 billion people had a mental health disorder, placing these among the leading causes of ill health and disability. Poor mental health can lower life expectancy . Global mental health (GMH) aligns most closely with Sustainable Development Goal (SDG) 3: Good Health and Well‐Being. The extent of the challenge around GMH is huge and requires innovation in how we understand and conduct GMH research, especially now given the human and economic cost of the Covid‐19 pandemic. Lancet Commission on Global Mental Health and Sustainable Development  broaden the GMH agenda to the general population; (ii) integrate the global response within other priorities and engage a wide range of stakeholders beyond health; (iii) target social and environmental causes; and (iv) make innovative use of non‐specialists to deliver mental health interventions and to mobilise the voices of those who suffer.The As a way of addressing these priorities, the present study explores if there had been opportunities, in principle, to embed psychosocial well‐being impact in research tackling global challenges across the range of SDGs: in short, to mainstream GMH. Our ambition is to trigger a step change in how the research community thinks about where, how and by whom mental health in LMICs can be impacted. To engage researchers, psychosocial well‐being impact must be deliverable without significant resource implications or overstretching expertise. Hence, we focus on opportunities for contained, yet meaningful, impact that can be undertaken as part of routine project activities. In so doing, we explore the potential for best practice in the application of psychology to the promotion of well‐being by a wide range of stakeholders in the field of GMH and implications for funding bodies who provide strategic direction and resources through financing this work.The World Health Organization WHO,  defines ScImago Country Rankings. The Global Challenges Research Fund (GCRF) is a £1.5 billion fund announced by the UK government in late 2015 to support cutting‐edge research that addresses the challenges faced by developing countries. The GCRF therefore plays a key role in determining the kinds of topics that are researched, the methods employed, and relationships cultivated between researchers in wealthier, research‐intensive nations such as the United Kingdom and scientists, practitioners and communities in LMICs. The importance of GMH was recognised in GCRF calls from the Medical Research Council (MRC) in 2017 and 2018 and from the Economic and Social Research Council (ESRC) with the Arts and Humanities Research Council (AHRC) in 2017. All supported multidisciplinary/interdisciplinary working, the MRC focusing on aetiology and epidemiology and the ESRC/AHRC on social and cultural insights.The United Kingdom is an interesting case study because it punches above its weight in the global scientific community, in third position after the United States and China in the 2020 We are particularly interested to leverage project activities analogous to participatory arts methods because there is a wealth of knowledge that arts methods can benefit psychosocial well‐being in LMICs  initiative led by Croucher, Evans, Greene and Wilson at the University of Bradford, UK, in partnership with Mercy Corps. As an aspect of public engagement, the team's initial GCRF‐funded research, Augmenting Jordanian Heritage, created opportunities through the use of three‐dimensional visualisations and printed models for refugees to handle virtually and manipulate objects representing heritage that had been destroyed or vandalised in recent conflict. Recognising the mental health impact of these activities, the team secured funding for GCRF project Building Resilience Wellbeing and Cohesion in Displaced Societies Using Digital Heritage. This second project is a novel interdisciplinary collaboration between archaeology, digital heritage, peace studies and international development. It uses heritage in an innovative way to enhance a sense of place and to explore the role and value of digital heritage in identity, community development and well‐being with conflict‐affected communities. Specifically, it enables people to discuss and use digital heritage for community confidence building, cohesion and psychosocial well‐being. These heritage‐oriented GCRF projects provide evidence of the potential for global researchers to impact mental health, and to learn to do so strategically, while delivering their core, non‐mental health, project aims.We take inspiration for our work from the In summary, we explore if there is potential to embed psychosocial well‐being impact in global challenges research where the primary aims are not mental health related. Our approach at this juncture is discovery oriented and descriptive, as opposed to hypothesis testing, given the current dearth of knowledge in this area. We anticipate our work contributing to the development of hypothesis‐testing research in the future. We examine information published by UK Research and Innovation (UKRI) to address our six research questions.Lancet Commission on Global Mental Health and Sustainable Development described above. The first two are as follows: (1) Where are GCRF funds allocated? (2) To what extent do GCRF projects self‐categorise as engaging with mental health? This information is important in establishing relevant context. Specifically, given the remit of GCRF to addresses the challenges faced by developing countries, it is important to know the relative position of mental health in terms of research interest and investment. Research Questions 3 and 4 address the potential of non‐mental health GCRF projects to engage psychosocial well‐being impact: (3) To what extent do non‐mental health GCRF projects engage implicitly with mental health ? (4) What were the opportunities to impact the psychosocial well‐being of target groups had only minor changes been made to the project? Our final two research questions are driven by the literature on participatory arts methods in LMICs: (5) Does the project involve any texts, objects or interactions between or enactments upon people? (6) To what extent might these create a focus to enhance psychosocial well‐being with target groups? Research Questions 3–6 allow us to establish if mental health impact, and potential for mental health impact, is being leveraged as effectively and strategically as possible in global challenges research as represented by the GCRF.Our first four research questions are driven by the priorities outlined by the https://gtr.ukri.org/). This is a searchable database allowing analysis of information on publicly funded UK research. GtR was the main source of data for our study and where other sources are used these are specified. GtR includes grants funded by the following organisations, all of which are independent, nondepartmental public bodies of the UK government's Department for Business, Energy and Industrial Strategy: AHRC, Biotechnology and Biological Sciences Research Council (BBSRC), ESRC, Engineering and Physical Sciences Research (EPSRC), MRC, Natural Environment Research Council (NERC), and Science and Technology Facilities Council (STFC). GtR was searched for information on GCRF grants from the start of the programme in late 2015 until the end of May 2020.To address these six research questions, we developed a data collection and analysis strategy to interrogate the UKRI gateway to research (GtR: https://public.tableau.com/app/profile/uk.research.and.innovation.ukri./viz/CompetitiveFundingDecisions2015-16to2019-20/UKRICompetitiveFunding. Table UKRI publishes data on competitive funding awards. Data for 2015–2020 (updated as of 18 November 2020) were found at Applications to the seven UK research councils are submitted via the online Joint Electronic System (JeS). During the grant submission process, at least one research area must be selected from a list provided indicating relevant subject area(s) or discipline(s). Each research area has subcategories from which more detailed terms can be selected. Applicants are instructed to select terms at the lowest appropriate level to describe the project. Qualifiers that further describe the area of study are grouped by type such as health category, approach, geographic area and theoretical methods. Applicants are instructed to select as many qualifiers as are relevant to enable understanding of the proposal. MRC applications have been largely brought into line with the other research councils. However, within the time frame of the data collection for this article, the relevant application classification is the health category qualifier only Table .f) ≤25 and, for MRC grants, health categories with f ≤ 20 were identified for the total sample of GCRF grants. These frequencies were decided through inspecting the GtR data and determining what would capture popular classifications while not overly narrowing focus. The most frequently used of these are as follows: (i) agricultural systems, (ii) natural resources, environment and rural development, (iii) anthropology and development and, for the MRC, (iv) infection and (v) generic health relevance.To establish what has attracted the most funding, research topics with frequency (f = 42), Asian and Middle Eastern studies (f = 30), development studies (f = 124), postcolonial studies (f = 30), and women's and gender studies (f = 26). The outcome of this thematic clustering was very similar to the six named GCRF strategic challenge portfolios, hence, serendipitously, reconstructing the programme structure. This demonstrates the close fit between the GCRF strategic challenge portfolios and funded GCRF research. It was decided therefore to use the portfolio titles to organise the GCRF‐funded topics  of GCRF grants were classified by applicants at submission as mental health related. Virtually all of these were via the MRC (N = 27), with the rest funded via joint AHRC/ESRC funding (N = 7), one via the AHRC alone and one (the present project) via EPSRC hosting of the Global Challenge Cluster programme.Although non‐MRC projects can be classified on submission under the ‘mental health’ health category, this is not displayed on the GtR grant summary page. A specific filter search was therefore conducted, which revealed that no non‐MRC GCRF grants were self‐categorised under the ‘mental health’ health category. Table f = 34), cities and sustainable infrastructure (f = 7), security, protracted conflict, refugee crises and forced displacement (f = 6), and education (f = 1) (Table f = 7), and cities and sustainable infrastructure (f = 6) .Our analysis reveals some interesting patterns in relation to the GCRF and GMH. GCRF funding allocation has been commensurate with its strategic challenge portfolios but under a relatively limited number of key research topics (23 of 610) and key health categories (5 of 23). Mental health is the third most frequently used MRC health category, but by a large gap, and in total only 3 per cent of GCRF grants self‐categorise as mental health related. These findings indicate very little emphasis on GMH in the programme and underscores the urgency of the work undertaken recently by the UK Department for International Development to formalise its position on, and approach to, the integration of mental health across diverse development sectors  global health and (ii) cities and sustainable infrastructure. Hence, where it has been engaged, GMH has tended to be situated in a biomedical model and/or to be framed within social policy and economic development. Mental health alignment with cities and sustainable infrastructure appears to engage many of the Mental health‐related grants were tangentially aligned with two GCRF strategic challenge portfolios: (i) security, protracted conflict, refugee crises and forced displacement, and (ii) education. With regard to the former, there is a mass of evidence that conflict and forced displacement can create multigenerational trauma and severely compromise the social networks through which communities build and sustain resilience  food systems and (ii) resilience to environmental shocks and change. This suggests that it may be even more difficult to argue for the relevance of psychosocial well‐being impacts in related fields. However, our coders agreed that 50 per cent of the former and 67 per cent of the latter projects sampled within these GCRF portfolios already engaged implicitly with the mental health of target groups.Having established the broader funding context, we now address our research questions regarding the potential that non‐mental health GCRF projects had, in principle, to embed psychosocial well‐being impact in their work.https://www.who.int/about/who-we-are/regional-offices). Where possible, closed  rather than active  grants were selected for completeness of available GtR information. Differentiation of lead organisation and research category was also sought. Most GCRF grants are research category ‘research grant’ (N = 1110) followed by ‘intramural’ (N = 64), ‘fellowship’ (N = 44) and ‘training grant’ (N = 6). A sample of 36 grants was identified in four steps  Table . Purposiant’ N = 110 folloTable Data consist of all the grant information available on GtR. Summary information for each grant has the following typical content: overview—title, funded value, funded period, funder, project status, project category, project reference, principal investigator, research subject (categories), research topic (categories), research programme (i.e. GCRF), abstract, technical summary and planned impact; organisations—lead organisation and collaborators; people—principal investigator, coinvestigator(s), cofunder(s) and project partner(s); publications (if available); and outcomes (if available)—artistic and creative products, key findings, impact summary, research tools and methods, collaboration, software and technical products, and engagement activities. A number of steps were taken to develop a template to guide and record data extraction of information available on GtR.Three sources were inspected for key types of mental health impact relevant to LMIC contexts AMS, . There eThe sampled grants were distributed randomly across a team of 14 academics such that the data extraction template was completed for each of the 36 grants independently by two coders. All but one of these academics has been involved in GCRF grants as a principal or coinvestigator. Their disciplinary backgrounds span: African studies; archaeology and heritage; community, health, and mental health psychology; counselling and psychotherapy; English and theatre; global health policy; international development; participatory arts; nursing; and social anthropology. Coder agreement is presented as a percentage given that the assessment task is relatively interpretative and was to explore possibilities rather than to determine certainties. Hence, following Glen , we set N = 2; food systems N = 3; global health N = 5; and resilience N = 1). For 19 grants (53%), both coders agreed that there was implicit engagement with psychosocial well‐being impact, and for six grants (17%), one of the two coders considered there to be implicit engagement. Hence, at least one coder considered there to be implicit engagement with psychosocial well‐being impact in 69 per cent of the sampled grants.Information in the completed data extraction templates to the question ‘To what extent do non‐mental health GCRF projects engage implicitly with mental health ?’ was tabulated into the form ‘no engagement’ and ‘engagement’. Coding agreement was strong at 84 per cent. For 11 grants (31%), both coders agreed that there was no implicit engagement with psychosocial well‐being impact , facilitate community building (83%) and preserve sociocultural identity (70%). Coding agreement was acceptable on opportunities for psychosocial well‐being impact on two of the psychological types: promote positive emotions (67%) and facilitate skills development (61%), and unreliable on positive sense of self (58%) Figure . Agreed Coding agreement was strong for the presence of people (75%) and objects (75%) and acceptable for texts (61%). Relative lack of confidence in identifying texts was reflected in that one of the coders of an additional 17 per cent indicated that they were ‘not sure’, compared with an additional 14 per cent for objects and only an additional 8 per cent for people Figure . Agreed From most to least frequent, agreed usability of type of material practice to create a focus to enhance psychosocial well‐being is as follows: people (64%), texts (36%) and objects (14%). When considered usable by at least one coder, this rises to 92, 69 and 22 per cent, respectively Figure . Coders In total, our analysis suggests that between 50 and 70 per cent of non‐mental health GCRF projects engage implicitly with psychosocial well‐being impact and each to have had at least one opportunity, in principle, to enhance the psychosocial well‐being of target groups. This supports that there is potential to embed psychosocial well‐being impact in global challenges research where the primary aims are not mental health related. Much of this work is already being done, likely unrecorded and, because implicit, is unlikely to be developed strategically for sustainable impact. Importantly, although mental health‐related grants were not aligned with two GCRF strategic challenge portfolios, i.e. (i) food systems and (ii) resilience to environmental shocks and change, coders agreed that 50 per cent of the former and 67 per cent of the latter projects sampled within these portfolios already engaged implicitly with the mental health of target groups.Opportunities for social well‐being impact (i.e. related to enhanced connections and community influence) were more reliably identifiable than opportunities for psychological well‐being impact . This could have been due to the restricted information available on GtR. On the other hand, it may have been easier to identify social well‐being impacts because the GCRF programme requires strong LMIC partnerships and collaboration. This is reflected in our finding that the social well‐being impacts of community mobilisation and of community building were the most frequently identified opportunities. Moreover, all projects were considered to have an opportunity to support community mobilisation and/or to facilitate skills development by at least one coder. More work is required to understand how opportunities for psychosocial well‐being impact can be identified in non‐mental health‐focused projects, particularly psychological impacts.To leverage mental health impact, we chose to explore the potential of participatory arts, conceptualised broadly as material practices, because we anticipated that a wide variety of GCRF projects presented opportunities to work with concrete things together. Importantly, when a material practice was present, it was usually considered usable as a focus to enhance psychosocial well‐being, especially when a project included interactions between people.cohesion and the social network lens on social capital . The three case studies were selected carefully as positive examples of opportunity to embed psychosocial well‐being impact in non‐mental health projects in principle, and the two for which interviews are available were selected from a corpus of 26 interviews conducted in the second phase of our work  security, protracted conflict, refugee crises and forced displacement, and (ii) education. With regard to the latter, Case Study 1 illustrates how educational organisations can be both the source and site of interventions to enhance the life chances of young people and the vitality of the communities served.Proposed activities of this project are described on GtR as aiming to support social cohesion and to ‘work against educational segregation by describing a more favourable picture of schools that educate pupils coming from more disadvantaged socioeconomic backgrounds’ (para. 3). To do so, policy documents were analysed, and local policy‐makers and researchers were interviewed about their views on value‐added measures ‘designed to make fair comparisons between schools […] by adjusting for various background factors and prior attainment by the individual child’ (para. 1). During fieldwork in Chile, the fellow ‘worked with local policymakers, particularly at the Ministry of Education and the Quality Agency in Education supporting government's thinking around innovative school accountability and school improvement methods to account for inequality when assessing school performance’ . Hence, the target groups of this project, which could be the focus of psychosocial well‐being impacts, were identified by the coders as school children and their families in Chile, and potentially other LMICs in the region. During interview, the fellow reflected on more potential beneficiaries, saying, ‘because most of the schools that are described and categorised as failures, usually head teachers and the whole community, they experience a lot of mental health issues’.The project was considered by coders to engage implicitly with the psychosocial well‐being of target groups through highlighting the contextual factors that can feed into value‐added statistics in Chilean schools as a means of reducing vulnerability, social exclusion and sense of failing associated with inequalities in the distribution of wealth. Both agreed that, had only minor changes been made to the project, there were opportunities to impact all six types of psychosocial impact Table . It was https://www.bristol.ac.uk/media-library/sites/policybristol/briefings-and-reports-pdfs/2017-briefings--reports-pdfs/PolicyBristol_Briefing_October_2017_Chile_Schools.pdf).In terms of material practices, both coders agreed that texts, including data sets, policy briefings and interviews with local policy‐makers and researchers, could have created a focus to enhance psychosocial well‐being with target groups. The fellow concurred: ‘my project wasn't thinking about well‐being or improving mental health as an impact but I could see, at the end of the project, the scope for that, especially after conducting the qualitative work’  global health, as might be expected, and, more interestingly perhaps, (ii) cities and sustainable infrastructure. Case Study 2 provides an example of how mental health impact has been embedded in the latter portfolio, framed broadly in terms of economic development.This project is described on GtR as bringing together ‘rural craft producers, fair trade businesses and design researchers in Indonesia to explore opportunities, to develop new networks, build long term partnerships and support innovation’ (para. 1). It is anticipated that ‘(t)hese initiatives will improve employment opportunities in rural areas, encourage pride in local culture, improve rural incomes and reduce pressures of migration towards cities’ (para. 3). Other producers ‘will also gain by meeting diverse craft practitioners which may stimulate thinking about new product possibilities that combine diverse skills […] building “linking” and “bridging” social capital’ (para. 8). Hence, the target groups of this project, which could be the focus of psychosocial well‐being impacts, were identified by the coders as craft producers, women and lower socio‐economic groups.One coder noted that, although framed very much as economic, the project engaged implicitly with the psychosocial well‐being of target groups through assisting craftspeople to develop self‐esteem and ability to project oneself and one's products. The other coder drew attention to implicit psychosocial well‐being impact of valuing local identity and culture. Both agreed that, had only minor changes been made to the project, there were opportunities to promote positive sense of self, facilitate community building and support community mobilisation of target groups. To do so, one coder suggested that the researchers could have asked questions about confidence, mutual support and collaboration. The other coder suggested that benefits to well‐being through increased financial security, valuing of local identity and social cohesion could have been stated more explicitly. However, they also noted how this small grant was already achieving a lot and would likely have needed some additional resource to adequately monitor psychosocial well‐being impact, although the in‐country partner organisations may have been already observing such benefits.In terms of material practices, both coders agreed that objects and people might have created a focus to enhance psychosocial well‐being with target groups. It was suggested that craft objects could be the focus for mutual celebration of creativity, although it was noted that these were already being used to increase sense of local pride in heritage. It was also suggested that there were massive possibilities for promoting understanding and empathy for migrant communities, and although enhanced social cohesion likely occurred, this could have been observed and discussed.Our findings demonstrate that mental health‐related grants were not aligned with two GCRF strategic challenge portfolios: (i) food systems and (ii) resilience to environmental shocks and change. However, coders agreed that 50 per cent of the former and 67 per cent of the latter projects sampled within these portfolios engaged implicitly with the mental health of target groups. Case Study 3 illustrates potential for mental health impact in relation to resilience to environmental shocks and change.This project was conducted with regard to rural communities of sub‐Saharan Africa who are vulnerable to climate‐related stressors and shocks through their dependency on agriculture and livestock. It is described on GtR as focused ‘on understanding the learning processes that build resilience and support livelihoods, which are responding to multiple pressures and opportunities across timescales in contexts that are complex and highly uncertain’ (para. 2). The target groups of this project, which could be the focus of psychosocial well‐being impacts, were identified by the coders as the vulnerable communities of the project case studies.One coder suggested that the entire focus of the project was community resilience and, by implication, engaged multiple facets of psychosocial well‐being. Interestingly, during interview, the PI interrogated the concept of resilience stating that ‘different people have different ideas of what resilience means and resilience to me does incorporate some mental health long‐term impact’. The other coder indicated that the project engaged implicitly with the psychosocial well‐being of target groups by using a social learning approach to map the ways vulnerable communities have access to climate information and share knowledge among themselves, how outcomes highlight the relationships between power and poverty, and how poor people, particularly women, suffer exclusion. The PI also reflected on a previous project illuminating these connections and giving him pause for thought about his role as researcher: ‘the reason they weren't interested in the long‐term, the seasonal forecasts was because the women‐headed households were the last in the pecking order to be able to use the communal ploughs. So knowing what the seasonal forecast was going to be actually was depressing for them […] so I sometimes wonder that I might not even be aware of some of the impacts I have on people’.Both coders agreed that, had only minor changes been made to the project, there were opportunities to secure all three types of social well‐being impacts, one stating it is likely that the project did facilitate community building, support community mobilisation and preserve sociocultural identity via their social networks approach, although this was not a target outcome and no data were reported.In terms of material practices, both coders agreed that interactions between or enactments upon people might have created a focus to enhance psychosocial well‐being with target groups. Specifically identified were the workshops to map social connections. Coders suggested that participants could have been asked explicitly about the psychosocial dimensions of community resilience. This could have included articulating which social connections are important to the community, how they might build‐on and protect them, and which are difficult and might be improved. The PI also expressed awareness that during research ‘sometimes the interaction can be quite negative. I think is what I was trying to point out around the mental health impact on the people that they work with. So it's not just about listening and saying, oh I've listened to you and people feeling better for that’. The other coder suggested that participants could have been encouraged to consider how they want to build and mobilise their community and to be more inclusive. It was recognised that something similar might have been done within the project but not mentioned explicitly. This is substantiated by the PI's comment that ‘there are potentially long‐term impacts of our interactions with people and they can be positive. I'd like to hope something I've done is positive’.This study explores if there had been opportunities, in principle, to embed psychosocial well‐being impact in research tackling global challenges across the range of SDGs, doing so through analysing grants funded by the UKRI GCRF. We provide evidence for policy‐makers, global challenge research funders and researchers that there are low hanging fruit opportunities to impact psychosocial well‐being across SDGs through routine project activities. The case is already being made strongly in relation to the development sector, but ‘(w)hile many development professionals recognise the need to do more for mental health, they do not always know where to begin’  and the pattern of projects funded by this programme constitutes a major focus of this article. The intention to conduct this work was articulated in our funding application, the GCRF has not been involved in the conduct of the research or consulted on outcomes prior to publication, and being funded by the GCRF has not knowing influenced the conduct of our study.This study was approved by the Ethics Committee of the School of Psychology, University of Leeds, UK, PSYC‐26, 21 April 2020.Figure S1. Coder agreement on opportunities for psychosocial well‐being impactFigure S2. Coding by type of psychosocial well‐being impact opportunity presentFigure S3. Number of types of psychosocial well‐being impact opportunity agreed present per projectFigure S4. Coder agreement on the presence of type of material practiceFigure S5. Coding by type of material practice presentFigure S6. Number of types of material practice agreed present per projectFigure S7. Types of material practice as a usable focus to enhance psychosocial well‐beingFigure S8. Number of types of material practice as a usable focus to enhance psychosocial well‐beingClick here for additional data file.


In the males of many vertebrate species, sexual selection has led to the evolution of sexually dimorphic traits, which often are developmentally controlled by androgen signaling involving androgen response elements (AREs). Evolutionary changes in the number and genomic locations of AREs can modify patterns of receptor regulation and potentially alter gene expression. Here, we use recently sequenced primate genomes to evaluate the hypothesis that the strength of sexual selection is related to the genome‐wide number of AREs in a diversifying lineage. In humans, we find a higher incidence of AREs near male‐biased genes and androgen‐responsive genes when compared to randomly selected genes from the genome. In a set of primates, we find that gains or losses of AREs proximal to genes are correlated with changes in male expression levels and the degree of sex‐biased expression of those genes. In a larger set of primates, we find that increases in indicators of sexual selection are correlated with genome‐wide ARE counts. Our results suggest that the responsiveness of the genome to androgens in humans and their close relatives has been shaped by sexual selection that arises from competition among males for mating access to females. Because sexual selection often drives the evolution of sexually dimorphic traits, the extent of sexual dimorphism across species can be used as an indicator of the relative strength of sexual selection, especially in systems where the mating competition is well understood  and how exclusively the genomic region is bound by a particular receptor over others   Hahn, . Furthercis‐regulatory elements. Typically, sexual selection acts more strongly in males and leads to male‐biased traits, such as ornamentation, weaponry, courtship, and sperm production, which are often regulated by androgens in vertebrates , a 15 base‐pair sequence composed of two palindromic  half‐sites separated by a three base‐pair spacer    with the highest binding affinity to the androgen receptor is called the canonical ARE (cARE), as well as an alternate to the canonical ARE (aARE) that differs at the end base pairs only  and an alternate SRE (aSRE), which bind generally to multiple corticosteroids , no comparable data were available for testis weight. Both body mass and canine height dimorphism were calculated using the residuals from a fitted log‐log model of male and female values for each species  across five organs  and numerous genes , we did not calculate significance of sex bias.To investigate genes and their association with AREs, sex bias, and androgen responsiveness, we used three datasets: one that reported a list of sex‐biased genes in humans  of both the genome‐wide count data for each motif and residual values for all three indicator traits . We then ran the exactmatch feature to produce a list of coordinates from the investigated AREs. We used a previously published custom R script  from all genes in the human genome 1000 times to generate two distributions. One distribution is the number of genes with at least one ARE within the predetermined distance ; the other distribution is the total number of proximal AREs in the entire set. We then determined where the male‐biased gene set falls on these distributions. We repeated this process for the androgen‐responsive gene list (n = 122). If AREs and genes with proximal AREs are overrepresented in the male‐biased and androgen‐responsive gene sets compared to the random distribution, then there is support for the importance of AREs in male‐biased expression and androgen responsiveness, respectively.We used a custom R script to extract gene coordinates from the human GFF file and then selected genes from this list that matched those that were male‐biased from the list of sex‐biased genes  where the phylogenetic effect's value (lambda) was freely estimated in the model, and (3) using a predetermined value of lambda, estimated using the phylosig function. We compared the Akaike Information Criterion (AIC) . We further estimated the correlation values by estimating the covariance with lambda set to the value determined by the appropriate model (no phylogenetic effect means lambda = 0) and converted those covariances to correlations. We calculated R2 from the chosen model.We identified 8250 orthologous genes with complete data across the five primates used for expression analysis. As with humans (described above), we generated a list of proximal AREs and their corresponding genes using the same distances for each species Table . We then Revell,  in R, wh Akaike,  of the tTo test for overrepresentation of any ARE motifs, we calculated a genome‐wide baseline for each motif by counting the number of hits in the genome in each species and taking the average of all five species to represent the genome‐wide group. For the proximal ARE group, we counted the number of each motif present in the set of 1312 genes. Because AREs were mostly conserved across species within genes, we only counted a motif once per gene. With a count table for genome‐wide and proximal AREs for each motif, we performed a chi‐square analysis to test for significantly different distributions. We then investigated the residuals for each motif to determine the percent contribution of each motif to the chi‐square statistic. If any motif had a large contribution to the differences between the two sets, we removed it and ran the chi‐square test again to confirm its effect.R2 from the chosen model.We downloaded the ultrametric tree for all of our 26 selected species from the 10k trees website to use as our phylogeny. As before, we created the three models using generalized least squares where the genome‐wide count of an ARE motif was treated as a function of each indicator of sexual selection. Using the chosen model, we looked at the significance of the effect of indicator on motif number both with and without Bonferroni correction for multiple tests of each indicator. As in the previous analysis, we estimated the correlation values and calculated nExp = 9). Second, we performed a principal components analysis and identified the principal component that had the largest number of loadings with the same directionality and explained a large amount of variance. We then took that principal component (PC ARE) and did the above‐described GLS modeling to determine its correlation with indicators of sexual selection. Using the 23 species with data available for all three indicator traits, we used canonical correlation analysis (CCorA)  for significantly correlated genes, whereas correlation coefficients range from 0.1 to 0.99  for at least one organ Tables . Most of99 Table . These dmvdp is strongly underrepresented for both the gene set with at least one proximal ARE and the gene set that passed the filters. In both cases, the residuals of mvdp strongly influence the distribution (∼20%) and removal of mvdp from the lists results in a lack of significance in the chi‐square tests . For the gene set with significant correlations between male expression values or sex bias and the number of proximal AREs, the motif p21 was strongly overrepresented, as the residuals greatly influence the distribution (47%) and removal of p21 from the list results in a lack of significance in the chi‐square test . Interestingly, mvdp has the most genome‐wide hits of any tested motif (range: 988–1255) and p21 has the fewest (range 47–66).Tests for over‐ and underrepresentation of specific AREs reveal the motif hklk, ccnd1, hk2), relative testis mass correlates with two , and body mass dimorphisms correlates with just one (psa3). The hklk motif count has a good model fit and a high correlation with both testis mass and canine dimorphism, as do hk2 and ccnd1 motif counts with canine dimorphism. Looking at the correlations between the genome‐wide motif counts and canine size, many motif counts have large correlation values  but lack statistical significance. The genome‐wide count of psa3 has a poor model fit and low correlation with body mass dimorphism and testis mass, whereas canine size has both high fit and correlation yet is not significant. Looking across indicator traits, motif counts with high correlational values in one trait tend to have high values in the other traits, even if these correlations are not significant in all or even one trait, especially when looking at canine size and testis mass. Two motif counts (cSRE and aARE) have a significant negative correlation with an indicator trait , but both have poor model fit and correlation values close to zero. Three motif counts have negative correlations with all three indicator traits: cSRE, mvdp, and slp2. In general, for body mass dimorphism the models describe low correlation values and poor model fit with motif counts, whereas for testis mass and canine dimorphism the models tend to have higher correlation values and better model fit with motif counts.Of the 18 studied ARE motifs, four motifs have at least one significant positive correlation between their genome‐wide counts and an indicator trait (Table nExp = 9), we find that more motif counts positively correlate with canine dimorphism  and relative testis mass  than expected by chance, but no excess of positive correlations exists for body mass . Principle components analysis of the ARE motif counts finds the first principal component explains 52.7% of the variance and has all but three motif counts  with positive loadings; two of these three motif counts have negative correlations with all three traits. No other component has as many loadings with the same directionality. This component (PC ARE) positively correlates with both canine size dimorphism and relative testis mass with a good fit and high correlation but does not correlate with body size dimorphism , it supports the finding of more positive correlations across motif counts than expected by chance. The correlation value for PC ARE and canine dimorphism is higher than that for PC ARE and testis mass, an observation that agrees with the general trend of higher correlations across individual motif counts for canine dimorphism. These results support the hypothesis that as genome‐wide ARE counts increase generally across motifs, there is a corresponding increase in some indicators of sexual selection.Using the binomial test, where the null expectation of positively correlated motif counts is half the total sampled motifs (F‐statistic indicates that dimensions one through three are significant (P = 0.0001), but dimensions two through three (P = 0.1097) and three by itself (P = 0.5930) are not. These results indicate a significant correlation between the indicator trait dataset and the genome‐wide ARE count dataset. Analyzing the CCorA without accounting for phylogeny finds no significant values despite lambda's small estimated value. All indicator traits are positive on the second component , three of which significantly correlate with an indicator trait, have positive loadings on both axes  generally have negative loadings on both axes. Species are divided such that Cercopithicoidae is separated from the Hominoidea and Platyrrhini along the second axis. In general, the first axis separates species by the amount of polygyny or precopulatory sexual selection and the second axis separates species by the amount of polygynandry or postcopulatory selection. The results of the multidimensional analysis are in agreement with the previous analyses, making the CCorA . Combined with the result of overrepresentation of p21 as a proximal ARE in the expression dataset, our observations suggest that these motifs may have an effect but their low rate of occurrence makes these effects hard to detect when compared to other motifs .Phylogenic signal in the CCorA Fig.  is estiment Fig.  with relxes Fig. . Four mo P = 0.590 are notcARE is at the center of the network from which the various motifs diverge  of the six motifs is correlated with an indicator trait. Considering motifs that had positive (cARE and pem2) or negative  loadings on the multivariate analysis did not reveal any new noticeable pattern. All of these findings considered together suggest a lack of any consistent evolutionary pressure on specific motif patterns.Using a haplotype network to show similarities between motifs, we find that the rge Fig. . The motfs Table  except fOur results reveal two general trends in primates. First, AREs are implicated in male‐biased, androgen‐responsive genes and the gain or loss of proximal AREs over evolutionary time can affect expression values and sex bias of these genes. Second, increasing numbers of genome‐wide AREs, along with an increase in sexual dimorphism in trait values, are indicative of sexual selection. Both trends can point to particular motifs that may have a significant effect on expression patterns or have genome‐wide counts significantly increase along with indicator traits. No pattern of motif nucleotide sequence, including those with high androgen receptor specificity, predictably influences correlations between traits and genome‐wide counts. When considered as a whole, the majority of AREs and the linear combination of AREs do increase in number along with sexual selection and gene expression. We conclude that individual motif sequences may not be as important to sexual selection as the overall trend in the number of motifs, which could allow for stronger sex‐biased regulation.r = 0.641, P = 0.001, R2 = 0.395, λ = 0.830), yet canine height has more significantly correlated motifs and more positively correlated motifs. Looking at the multidimensional analyses, body mass dimorphism has little influence on the distribution of ARE motif counts. Instead, canine height dimorphism has a large influence on the distribution of ARE motif counts. If both body size dimorphism and canine size dimorphism are indicators of sexual selection and are correlated, why does genome‐wide ARE motif count have a strong signal in one (canine) but no discernable signal in the other (body size)? It is important to note that these traits are approximations for sexual selection and carry assumptions that may not truly reflect the direct influence of the trait on reproductive success  or canine height (P = 0.981) sexual dimorphism, suggesting independent effects of pre‐ and postcopulatory selection  is the main target of selection, suggesting that different clades might favor alternate motifs depending on their evolutionary histories. Ultimately, an analysis of additional genomes across a wider array of organisms will better elucidate the evolutionary response of genome‐wide ARE motif number to an increase in sexual selection intensity. Given these findings, there is a clear need to further investigate the role that AREs and other noncoding DNA elements play in evolutionary responses to natural and sexual selection.APA conceived the project, collected the data, performed the analysis, designed the figures, and wrote the manuscript. AGJ conceived the project and wrote the manuscript.The authors declare no conflict of interest.https://github.com/AndersonDrew/Primate_ARE.All relevant R code and data tables can be accessed in the Supporting Information and at Associate Editor: T. ConnallonHandling Editor: A. G. McAdamSupporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.


Arthroplasty is an effective, yet costly, surgical procedure for end‐stage osteoarthritis. Shorter stays in hospital are being piloted in Australia. In some countries, short stay is established practice, associated with improving perioperative care and enhanced recovery after surgery practices. Exploring the acceptability to patients of a short stay care pathway in hospital postarthroplasty is important for informing health policy, adoption and potential scalability of this model of care.Consecutive patients at one site, at least 3 months post total joint arthroplasty, were invited to participate in theory‐informed semi‐structured qualitative interviews. The Theoretical Framework of Acceptability (TFA) informed development of the interview guide. Interview data were analysed using the Framework Method.Eighteen patients were invited. Fifteen consented to be contacted and were interviewed. Short‐stay post arthroplasty was highly acceptable to patients who had the supports necessary to recover safely at home. Key findings were as follows: flexibility of short‐stay care pathway was essential and valued; prior beliefs and expectations informed acceptability; and the absence of out‐of‐pocket expenses had an incentivizing effect, but was not the primary reason for patients choosing this care pathway. Further themes analysed within the TFA constructs highlighted nuances of acceptability relating to this model of care.A short stay in hospital post arthroplasty appeared to be acceptable to patients who had experienced this care pathway. Our thematic findings identified aspects of the short‐stay care pathway that enhanced acceptability and some aspects that limited acceptability. These findings can inform refinement of the short‐stay care pathway.Patients/people with lived experience were not involved in the study design or conduct of this preliminary work; as this short‐stay model of care was recently introduced, only a small group of patients was eligible to participate in this study. This study is the first step towards understanding the experiences of patients about a short‐stay model of care post arthroplasty. The findings will help inform future patient and public involvement in expanding the programme. The study setting was a single site in Melbourne, Australia, which was the first site where this short‐stay care pathway was routinely offered in the state of Victoria. The researchers approached this study through an interpretivist paradigm, paying attention to people's perspectives in context.2.3The ‘short‐stay care pathway’ is a complex intervention. A detailed description of the short‐stay care pathway was mapped to the Template for Intervention Description and Replication (TIDieR) checklistShort stay in hospital typically involves a planned hospital admission of one night or, in some cases, same‐day discharge. The short‐stay care pathway is offered only to eligible patients based on thorough clinical assessment by health professionals. In Australia, another component of the pathway is a ‘no gap’ financial arrangement, whereby the cost of surgery and associated fees  are set and covered in full by the health insurer.2.4Patients who experienced a short stay in hospital after arthroplasty before May 2021 were consecutively identified. At the time of data collection, selecting this date (May 2021) allowed for at least 3 months postsurgical recovery. Patients who were unable to converse in English, or employees of the health insurer (Medibank) or private hospital  were not eligible to participate. Eligible patients were contacted by an administrative staff member of the surgical consulting rooms who briefly outlined the aim of the study using a script provided by the research team and who obtained agreement to be contacted by the research team. A member of the research team (C.M. or C.P.) then discussed the study with the patient, provided the patient information and consent forms, explained the reasons for conducting the study, described the interviewer's experience and clinical background and answered any questions. Written or audio‐recorded verbal informed consent was obtained before commencing the interview. Recruitment ceased when the target sample of 15 participants was reached, which was determined by published guidance on sample sizes for theory‐based interview studies2.5Semi‐structured interviews were conducted using distance modes  to allow for COVID‐safe practice, minimize participant burden and allow recruitment of patients who lived in regional areas. All interviews were conducted by authors C.M. and C.P. . The interview guide  were analyzed using an inductive, and then a deductive, approach within the Framework Method.2.7The following steps contributed to rigor in the design and conduct of this study. First, the interview questions were ‘back coded’3Of the 18 patients (6 THR and 12 TKR) invited to participate, 15 consented and were interviewed  : The flexibility of the short‐stay care pathway was noted by participants as being essential and valued. Many examples where the care plan was modified slightly to suit or respond to their individual needs were shared. Some of the examples indicate small changes to the planned care pathway such as offering additional home cleaning services or relocating physiotherapy appointments to the workplace instead of at home. Other reported examples of changes to the care pathway were substantial. For example, some participants were not able to be discharged home as planned for different reasons.We're all different and in my case, it probably wouldn't have been an idea to go straight home because of the blanking business [referring to postural hypotensive episodes post‐surgery] that I was having.Marie (TKR): In these cases, depending on their circumstances, participants either remained in hospital for an additional night and then were discharged home, or were discharged to inpatient rehabilitation.The short‐stay care pathway was occasionally modified according to the needs of the individual following discussions with staff. This flexibility was perceived to influence multiple constructs of acceptability, including how effective they thought it was (perceived effectiveness), how they felt about it (affective attitude) and how much effort was required to participate (burden).3.1.2When you're at home, you can just be fully relaxed…And yeah, I just think that also makes the recovery of the patient a lot, lot quicker and a lot better.Ryan (TKR): Participants appeared to have strong opinions and prior beliefs about the consequences of home‐based recovery versus inpatient rehabilitation. These opinions and prior beliefs appear to have influenced perceived acceptability of the short‐stay care pathway.So the less time in the hospital probably the better. I understood the process of, the quicker you get back on your feet and get moving, the quicker the recovery.Richard (TKR & THR): Adding to these prior beliefs about a short stay in hospital after arthroplasty was how informed a participant was in terms of the potential risks of being admitted to hospital and/or the potential benefits of recovering at home.But also apart from everything else, you're just not well enough to come home … you're just not well enough. Crazy idea.Rose (TKR): Participants' expectations of their recovery from arthroplasty also influenced whether they thought it was acceptable to have a short stay in hospital. An example of this association was where participants described arthroplasty as ‘major surgery’. Participants who perceived arthroplasty as major surgery, but expected that they could recover well at home, thought that a short stay in hospital was acceptable. By contrast, participants who expected that major surgery would require inpatient care to effectively recover did not perceive a short stay in hospital as acceptable.Expectations of the short‐stay care pathway were positively influenced by the ‘joint school’ (preoperative education sessions) and preadmission appointments. These information sessions influenced the acceptability of a short stay for participants who were predisposed to the short‐stay pathway. Participants' prior beliefs and expectations of a short stay and recovering at home impacted on many constructs of acceptability, such as perceived effectiveness, safety, affective attitude, ethicality and self‐efficacy.3.1.3I was very pleased to be offered this. I thought it was a very good plan… But I was very grateful they did [offer the ‘no gap’] because it meant that I could have my surgery.Rose (TKR): The ‘no gap’ component of the short‐stay care pathway ‘persuades’ people to undertake a short stay in hospital. For some people, the financial arrangement was fundamental to accessing the programme and was therefore highly persuasive.But I guess, it's sort of the icing on the cake to find that you don't have to pay extra for sure. No doubt about that…So, I wouldn't say that was the clincher, but it certainly didn't hurt.Thomas (TKR): A subgroup of participants changed their health insurance provider to access this programme, which is also indicative of the incentivizing effect of the ‘no gap’ arrangement. Other participants wanted to have a particular surgeon, a particular surgical procedure  or access a particular hospital .  For these participants, the ‘no gap’ arrangement was an important additional incentive.In one negative case, the ‘no gap’ arrangement was not perceived as influencing their decision to proceed with the short‐stay care pathway. This theme illustrates that people engaged with the short‐stay programme for different reasons; however, it reinforces that the ‘no gap’ arrangement was an appreciated and valued incentive. The ‘no gap’ arrangement influenced multiple constructs of acceptability including burden, affective attitude, ethicality and perceived effectiveness.3.2Section 3.2.1Comprehensive ‘package’ of care with skilled staff at the core was strongly linked to perceived effectiveness. Theme 2: Before and after—outcomes of surgery make it all worthwhile indicated that the positive clinical outcomes after arthroplasty were reported as a primary reason for perceiving the surgery and recovery as worthwhile. Theme 3: Home‐based care can accelerate recovery highlighted that recovering in a comfortable and familiar environment contributed to perceptions of the short‐stay model of care as effective.Three themes demonstrated that perceived effectiveness was a strong driver of acceptability for this intervention: Theme 1: 3.2.2Anxious and trepidatious about unknowns, participants felt anxious or apprehensive before surgery and discharge home because they wondered if they would recover and manage well. Theme 2: Positive feelings during recovery and individualized care were expressed by participants.Theme 1: 3.2.3alleviates financial burden. Participants described ‘burden’ in this context as relating to both financial costs and emotional worry. Theme 2: Managing recovery and advocating for needs represents participants' acknowledgement that some effort was required to manage their recovery at home and (on occasions) to advocate for their needs. Theme 3: Handing over responsibilities to support people at home represented the burden that fell to carers and support people.Theme 1: ‘No gap’ 3.2.4Short‐term reduction in participants' independence and activities, which was anticipated during recovery from surgery and therefore did not detract from the acceptability of the care pathway overall. Theme 2: Benefits of home‐based recovery such as less travel time  and sleeping better in their own bed were highlighted by participants who recovered at home.Theme 1: 3.2.5Effective use of available resources was a notion identified by participants who perceived that a short stay in hospital aligned well with their values as it would ‘free up’ hospital beds for people who needed them and thus represented an effective use of finite healthcare resources. Theme 2: Financial ‘fairness’ and access was attributed to the ‘no gap’ arrangement. Participants believed that this ‘fair’ arrangement allowed access to private surgery for some people who otherwise may be unable to afford the out‐of‐pocket fees typically incurred with private surgery.Theme 1: 3.2.6Adequate support to cope physically and emotionally at home influenced participants' confidence and whether they felt able to and/or did cope at home. Theme 2: Feeling informed and making progress were described by participants who felt informed following consultations with health professionals, which instilled confidence about their surgery and recovery. When participants perceived that they were making ‘good’ progress after surgery, this further contributed to a sense of self‐confidence to manage at home.Theme 1: 3.2.7Variable understanding of the ‘short stay’ in the pathway was identified, including differing understanding of the estimated hospital stay duration and what recovery at home would involve. Some participants felt well informed, whereas others felt surprised and unprepared for discharge after one night in hospital. In contrast, participants clearly articulated a strong understanding of the arthroplasty procedure and the ‘no gap’ arrangement. Theme 2: Knowing the risks and benefits of inpatient versus home‐based recovery influenced acceptability of the short‐stay care pathway. Participants who recounted knowledge of the potential risks of staying in hospital  explained that this was an important factor driving their preference to recover at home.Theme 1: 3.2.8Critical timepoints for clinical and safety assessments were highlighted by participants. Participants perceived that thorough clinical monitoring and assessment was critical to their safety, especially during the early phases of recovery at home. This theme was supported by examples shared by four participants who developed postoperative complications at home , who stated that they felt these complications may have been detected earlier with closer monitoring. Theme 2: Support at home enhanced safety reflected participants' perceptions that sufficient support at home enhanced their safety after discharge.Theme 1: 4This Australian study explored the acceptability of a short‐stay care pathway post arthroplasty from the perspectives of patients. We found that this pathway was highly acceptable for patients who had been carefully assessed and had the supports necessary to recover safely at home. As the more detailed results  were integral to perceived effectiveness of the short‐stay care pathway for participants. This is similar to findings of a study with patients after pilonidal sinus surgery, whereby acceptability was associated with recovery outcomes.4.1Issues related to perceived safety during the early phases of recovery at home were identified and affected acceptability. Some participants identified early signs of postoperative complications soon after discharge , which they thought did not receive timely review as per the planned pathway. In most of these cases, participants were resourceful and initiated review with their own general practitioner. These cases indicate that changes in postoperative surveillance and intervention may further increase acceptability.As these findings also suggest that in surgical contexts perceived safety and risk may impact acceptability, other researchers using the TFA may wish to consider including the construct of ‘perceived safety and risk’. Further investigation as to whether perceived safety and risk impacts on acceptability of interventions in other surgical and nonsurgical contexts is warranted.Further opportunities for improving acceptability of the short‐stay care pathway were identified in relation to holistic preoperative screening. Adequate support at home to be able to manage was important to participants. Adequate support included a capable caregiver or support person able to provide physical assistance with activities of daily living and, in some cases, emotional support. This indicated that closer, comprehensive preoperative screening of patients' living arrangements and the level of support available at home may benefit acceptability. At least one participant in our sample strongly believed that recovery at home was unsafe and that inpatient rehabilitation would aid their recovery. In an Australian study exploring the acceptability of different modes of rehabilitation, Buhagiar et al.Participants' understanding of the ‘short stay’ component of the care pathway varied, and uncertainty undermined acceptability. Participants had a strong understanding of the arthroplasty procedure, which suggests that information provided about this stage of the care pathway was comprehensive and generally well understood. In contrast, participants demonstrated variable understanding of the ‘short‐stay’ component. Despite strong evidence that home‐based rehabilitation is safe and effective,As previously described, we used Sekhon et al.'s4.2The strengths of this study include use of the TFA to inform the study design. The use of theory‐informed approaches in implementation research is strongly advocated.Another strength of this study was the initial inductive analysis, which allowed the research team to consider acceptability across the TFA constructs, identify relationships between some constructs and explore factors outside the constructs that might be associated with acceptability.Although steps were taken to reduce sampling bias , the sample did not include any self‐employed participants and included only two casual or part‐time employed participants. This may limit the range of perceptions obtained particularly related to the opportunity cost construct as participants in our sample did not appear concerned about having to take time off work during their recovery period. Further, only English‐speaking participants were included. Therefore, these findings may not reflect the experiences of patients from culturally and linguistically diverse backgrounds, which warrant further investigation.delivering the intervention.Only the perspectives of those who received the intervention were obtained for this study. Implementation success is also proposed to be linked to the perceived acceptability of those 5Patient acceptability of a short stay in hospital postarthroplasty was conditional on a range of factors such as skilled and caring staff, comprehensive care, adequate support to manage at home and perceived positive clinical outcomes post arthroplasty. The addition of a financial arrangement that eliminated out‐of‐pocket expenses incentivized this model of care and contributed to its acceptability for some patients. Potential areas for improving the acceptability of this care pathway were identified. Overall, patients found this short‐stay model of care acceptable.Research Assistant salaries for Cassie McDonald and Camille Paynter were funded by the research grant originally from the Medibank Better Health Foundation. Daevyd Rodda contributed to the development of the model of care being studied. Daevyd Rodda and Dwane Jackson are financial beneficiaries of surgeries performed under this model of care at Vermont Private Hospital. David Story has received previous research grants from the ANZCA Research Foundation, including some with original funding from the Medibank Better Health Foundation. Jill Francis has received previous research grants from the ANZCA Research Foundation. Other authors have no conflict of interest to declare.Ethics approval was granted by the University of Melbourne Office of Research Ethics and Integrity .Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.Supporting information.Click here for additional data file.


This retrospective cohort study aims to describe patterns of rotational thromboelastometry (ROTEM™) results in paediatric trauma following the implementation of a ROTEM‐guided critical bleeding algorithm and major haemorrhage protocol (MHP).This retrospective observational study was conducted in a tertiary trauma hospital in Queensland, Australia, where point‐of‐care ROTEM was introduced for paediatric patients in 2014. All children aged less than 18 years who had a ROTEM test during their presentation between January 2014 and December 2017 for a traumatic injury were included in the dataset. Other children with a record in the hospital's trauma registry in the same period were also screened for blood product usage. Data were collected for frequency of ROTEM testing, pathology and ROTEM results, blood product and antifibrinolytic use along with injury related data. Compliance with recommended treatment thresholds for detected coagulopathy was also reviewed.A total of 1039 children were listed in the trauma registry, including 167 children having a ROTEM test for trauma. Factors significantly associated with having a ROTEM test were older age, higher injury severity score (ISS >12) and penetrating injury. A result exceeding a treatment threshold was returned for 122 (73.1%) of 167 children, with hyperfibrinolysis identified in 88 (52.6%) of 167 and hypofibrinogenaemia identified in 54 (32.3%) of 167. Adherence with the recommended treatments for those children where a treatment threshold was exceeded was low in this cohort.The use of ROTEM‐guided blood component replacement is an emerging practice in children for both traumatic and non‐traumatic bleeding. Targeted replacement of identified coagulation defects guided by rapid point‐of‐care testing is an emerging alternative to fixed‐ratio‐based protocols. Further research is required to validate treatment thresholds in the paediatric population and further investigate the clinical outcomes for patients as a result of early correction of trauma‐induced coagulopathy. The use of ROTEM‐guided blood component replacement is an emerging practice in children for both traumatic and non‐traumatic bleeding.This cohort demonstrated high levels of fibrinolysis across all injury severities and across different regions of injury. This may represent different pathophysiological pathways or be due to different injury patterns in children compared to adults and is worthy of prospective investigation.Further research is required to validate thresholds for factor and blood product replacement in the children and evaluate clinical outcomes as a result of early correction of trauma‐induced coagulopathy.Trauma causes 40% of child deaths in high income countries, with haemorrhage being a leading cause of death in this population.Major haemorrhage protocols (MHP) remain an important part of haemorrhage management, but they have been slower to appear in the paediatric literature.Over recent years, there has been an increasing interest in targeted transfusion guided by point‐of‐care VHA.Developing an evidence base for more targeted transfusion strategies within the paediatric setting has implications for effective management of TIC, reducing transfusion related complications for patients, and for improved rationing of scarce blood products. The use of VHA is not yet standard practice in the adult or paediatric trauma setting but has increasing popularity in many regions. In other areas of paediatric practice, particularly cardiac surgery, VHA‐guided transfusion is standard care in many centres.The Gold Coast University Hospital (GCUH) ED introduced a point‐of‐care rotational thromboelastometry (ROTEM™) into the critical bleeding algorithm for paediatric patients in 2014 Fig.  and any The aim of this retrospective observational study was to review ROTEM results and the rates of targeted treatment for abnormal results in a paediatric trauma population following the implementation of a ROTEM‐guided critical bleeding algorithm. Data were analysed by injury severity and region of injury and compared to standard laboratory coagulation results.This retrospective observational study was conducted at GCUH in Queensland, Australia. GCUH is a tertiary trauma referral hospital in Queensland, Australia, with over 1500 trauma presentations per year with approximately 350 (23.3%) being major trauma with an Injury Severity Score (ISS) of greater than 12. Over the study period, 1039 paediatric trauma presentations were recorded, with 103 scoring an ISS of greater than 12 (9.9%).All children aged less than 18 years old who received a ROTEM test during their presentation between January 2014 and December 2017 for a traumatic injury were screened for inclusion, those with traumatic injuries were included. Other children presenting during the time period with a record in the hospital's trauma registry were also screened for antifibrinolytic and blood product usage. All children who meet ‘Trauma Alert’ or ‘Trauma Respond’ criteria Fig.  at triagData were collected retrospectively from pre‐hospital, ED and inpatient records, laboratory records and the trauma registry. Data included, but were not limited to patient demographics, ISS, laboratory results from blood tests, and all blood and blood product usage  during their hospital admission.2 test was used to determine significant differences between ROTEM testing groups, with a P < 0.05 considered statistically significant. ROTEM results were assessed according to the algorithm for each of the algorithm's four treatment thresholds ; each child's results were classified as meeting or not meeting treatment threshold. ROTEM results were compared for children with more severe injuries (classified as ISS 12 or higher) to those with ISS <12. The first available blood results , collected after the child's triage date, were extracted from the laboratory information system. The t‐test was used to compare means of normally distributed variables and the non‐parametric Mann–Whitney U‐test was used to compare distributions of nonparametric variables. A Pearson product‐moment correlation coefficient was computed to assess the relationship between laboratory fibrinogen and ROTEM FIBTEM A5.Simple descriptive statistics (proportions) were produced for children who received ROTEM, and those from the trauma registry who did not. The χThis study was reviewed by the HREC committee and deemed a quality improvement initiative, not requiring ethics committee approval (LNR/2019/QGC/52798). The study is reported according to the STROBE guidelines.A total of 1039 children were listed in the trauma registry, including 167 children who had a ROTEM test for trauma during the period. Factors significantly associated with receiving a ROTEM test were older age, a higher ISS (ISS >12) and a penetrating injury (Table Most children with a ROTEM test had their first ROTEM test collected in ED (94.6%), particularly for those with less severe injuries ISS <12) (Table  (Table 2P = 0.026). Injury to multiple body regions and isolated head injuries were also more commonly associated with hypofibrinogenaemia when compared to mild/moderate injuries . There were also no significant differences in detected hyperfibrinolysis when analysed by region(s) of body injury  of 167 children, with hyperfibrinolysis identified in 88 (52.6%) of 167 and hypofibrinogenaemia identified in 54 (32.3%) of 167. Hypofibrinogenaemia was more likely in children with severe injuries  compared to less severe injuries  had a ROTEM performed before replacement. Similarly in those who received platelets or FFP, a ROTEM was performed prior to administration in all patients. There were no patients treated with platelets or FFP without a ROTEM being performed, unless they were administered prior to arrival to our centre, as part of an interhospital transfer.r = 0.68, P < 0.01, Fig. Fibrinogen result by ROTEM (FIBTEM A5) was well correlated with the first fibrinogen result on a blood test (The use of VHA in paediatric trauma and major haemorrhage is an emerging practice. Audits of paediatric practice in centres with access to VHA reported its use in less than 50% of paediatric cases.This cohort demonstrated high levels of fibrinolysis across all injury severities and across different regions of injury. This finding is consistent with previously published data reporting hyperfibrinolysis occurring more commonly in children when compared to adults.The exact incidence of hyperfibrinolysis in adult trauma remains elusive and has not been definitively established; however, the estimated frequency ranges from 3 to 20%.The difference in incidence of hyperfibrinolysis is worthy for further prospective multisite data collection to exclude selection bias as a contributor to this observation. Further exploration of pathophysiological mechanisms that may further explain this observed difference between children and adults is also warranted to better understand the balance between physiological and pathological fibrinolysis and guide the development of treatment thresholds. In addition, studies into the empiric use of TXA in paediatric trauma focused on long‐term patient‐centred outcomes are warranted. Future prospective studies could investigate the roles of plasminogen, tPA and PAI‐1 in children, which may contribute to this finding.Incidence and patterns of hypofibrinogenemia in this cohort are consistent with previously published data.The role of hypofibrinogenemia and its treatment in isolated head injuries is controversial in both adults and children. In adult patients with isolated head injury, low fibrinogen on ROTEM has been described as an early indicator of severe injury and predictor of mortality.There was low compliance with suggested treatments detailed on the critical bleeding algorithm when a patient met the treatment threshold in this cohort. The decision to administer blood products to an individual patient is a multifactorial decision‐making process based on the immediate needs and clinical situation the clinician encounters, while optimal adherence to a protocol is theoretically ideal the protocol cannot always be applied in every situation. In our centre, evaluation for TIC by ROTEM will continue and be encouraged for children presenting with major trauma and where there are concerns for bleeding. Ongoing acquisition of data and gained experience may assist clinical decision making and guide specific antifibrinolytic and/or blood product therapy, minimising exposure to unnecessary products in injured children.This retrospective review is limited by the data that was entered and available from the electronic systems available. Cross‐referencing records from multiple systems were undertaken to minimise missing or inaccurate data. Aspects of clinical care and clinician decisions regarding administration of blood components or treatment could not be determined from the written notes in most cases. Similarly, the presence or clinical suspicion of clinically relevant bleeding is often difficult to determine from retrospective review of the notes. Where possible pre‐hospital data on the administration of TXA and blood products have been included; however, prehospital records were not available for all patients. Changes in clinician familiarity with the MHP may have occurred over the recruitment period; however, no significant differences in patterns of product usage or compliance with the algorithm were detected. As a retrospective convenience sample, this cohort is not adequately powered to detect changes in clinical outcomes related to adherence to recommended treatment thresholds.The use of ROTEM‐guided blood component replacement is an emerging practice in children for both traumatic and non‐traumatic bleeding. Targeted replacement of identified coagulation defects guided by rapid point‐of‐care testing is an alternative approach to fixed‐ratio‐based protocols. In our centre, evaluation for TIC by ROTEM will continue and be encouraged for children presenting with major trauma and where there are concerns for bleeding. Ongoing acquisition of data and gained experience may assist clinical decision making and guide specific antifibrinolytic and/or blood product therapy, minimising exposure to unnecessary products in injured children. Further research is required to validate treatment thresholds in the paediatric population and further investigate the clinical outcomes for patients as a result of early correction of trauma‐induced coagulopathy.Figure S1. GCUH trauma alert and respond activation criteria.Click here for additional data file.


In the case of a 62‐year‐old man with biopsy confirmed primary diffuse large B‐cell lymphoma of the CNS treated with methotrexate, cytarabine, thiotepa and rituximab (MATRix) chemoimmunotherapy and busulphan/thiotepa autograft, follow‐up contrast enhanced magnetic resonance imaging (CE‐MRI) demonstrated ongoing peripheral enhancement at the site of original lesion (middle left). Here we show that treatment response assessment maps (TRAMs) can be used to differentiate active disease from benign enhancement.‘Red’ regions have retained and ‘blue’ regions cleared contrast; contrast clearance is associated with active disease. TRAMs efficacy in discriminating viable lymphoma from post‐biopsy change at baseline is shown in another patient by the right sided images. In the case of this 67‐year‐old man, with biopsy proven primary CNS lymphoma, it is not possible to distinguish post‐biopsy change from possible remaining macroscopic lymphoma on the top right CE‐MRI. The bottom right TRAMs however discriminates the MRI findings into blue (viable lymphoma) and red (post‐biopsy benign) changes.Gadolinium enhancement is a feature of active lymphoma, but contrast enhancement is not specific as it is also seen following disruption of the blood brain barrier due to biopsy, inflammation and haemorrhage. With TRAMs, further magnetic resonance images are acquired approximately an hour post‐contrast administration and subtracted from the initial images providing a colour map. In the present case, the lesion (top left) had residual peripheral contrast enhancement following treatment (middle left). The red signal on TRAMs (bottom left) though indicates benign enhancement, enabling a decision not to proceed to radiotherapy. To the best of our knowledge the patient is still in complete remission nearly two years post‐imaging.Early work has been published in some tumour types, however, to our knowledge this is the first report describing TRAMs as a new concept in CNS lymphoma. TRAMs has potential as a problem solving tool in CNS lymphoma as it allows MRI contrast enhancing regions to be stratified into areas of viable lymphoma and benign enhancement, increasing accuracy of the staging and response assessment used to guide patient management decisions.


Spontaneous extradural hematoma in Sickle cell disease is rare neurological complication with few cases reported in the English literature. We report a case of a 16‐year‐old male patient who was previously diagnosed with Sickle Cell Beta Thalassemia and presented with severe headache and vomiting for 3 days. An emergency CT scan of the head demonstrated right‐sided acute parietal extradural hematoma with mass effect. Patient underwent emergent craniotomy with evacuation of the hematoma. Patient recovered completely. Although calvarial infarction has been associated with extradural hematoma, an absence of it makes our case distinct. A high index of suspicion should be made in SCD patients for possibility of EDH in progressive headache. Although neurological complications are rare in SCD patients in the Asian population, progressive headache should be investigated for associated neurosurgical emergencies in the targeted population. The inheritance can be in the homozygous state (Hb SS) or compound heterozygous state where an association with another globin gene mutation is noted. Global variation in the cases of SCD is noted with highest frequency noted in the sub‐Saharan Africa, central India, and the Middle East.2A 16‐year‐old male patient previously diagnosed with Sickle Cell Beta Thalassemia who was on hydroxyurea presented with history of severe headache and vomiting for 3 days. Although there was past history of vaso‐occlusive crisis in the patient, history of antecedent trauma was not given. On physical examination, patient was conscious and oriented with no any localizing signs. An emergency computed tomography (CT) scan of the head was performed which demonstrated a hyperdense blood attenuation extradural collection in the right temporal region with mass effect and effacement of ipsilateral lateral ventricle and sulcal spaces Figure . No evid3Sickle cell disease (SCD) and its variants encompass a group of autosomal recessive disorders resulting from a single nucleotide polymorphism in the beta globin gene. Although considered rare in Nepal, recent studies have demonstrated increased prevalence of SCD as well as SCD along with other genetic hemoglobinopathies such as beta Thalassemia.Central nervous system involvement is the most dreaded manifestation of SCD with significant morbidity and mortality. The various manifestations include chronic headache, epilepsy, ischemic or hemorrhagic stroke, cognitive impairment due to chronic anemia, Moyamoya disease, hypoxia, and silent infarcts.Spontaneous extradural hematoma is a rare complication of SCD with few cases reported in the literature.4Although neurological complications are rare in SCD patients in our region, it is instrumental in investigating individuals presenting with severe headache for a possible neurosurgical emergency. Furthermore, a possibility of SCD needs to be ruled out in targeted population presenting with neurosurgical emergencies.All authors have participated in writing and reviewing the manuscript.The authors declare that they have no competing interests.Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.