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This paper explores and charts the reasons why some primary school headteachers in "disadvantaged" London schools remain in post at a time of rising rates of attrition of school leaders and headteachers. Instead of exploring the reasons why headteachers are quitting their posts in urban schools, this study examines the retention issue from an alternative perspective by understanding what factors encourage headteachers to stay. Findings suggest that the London headteachers are fueled by their commitment to principles of social justice and demonstrate this by providing stability and security for the children and staff in their schools.

Cyclophilin A (CypA), the cellular receptor of the immunosuppressant cyclosporin A (CsA), is an abundant cytosolic protein and is involved in a variety of diseases. For example, CypA supports cancer proliferation and mediates viral infections, such as the human immunodeficiency virus 1 (HIV-1). Here, we present the design of PROTAC (proteolysis targeting chimera) compounds against CypA to induce its intracellular proteolysis and to investigate their effect on immune cells. Interestingly, upon connecting to E3 ligase ligands, both peptide-based low-affinity binders and CsA-based high-affinity binders can degrade CypA at nM concentration in HeLa cells and fibroblast cells. As the immunosuppressive effect of CsA is not directly associated with the binding of CsA to CypA but the inhibition of phosphatase calcineurin by the CypA:CsA complex, we investigated whether a CsA-based PROTAC compound could induce CypA degradation without affecting the activation of immune cells. P3, the most efficient PROTAC compound discovered from this study, could deplete CypA in lymphocytes without affecting cell proliferation and cytokine production. This work demonstrates the feasibility of the PROTAC approach in depleting the abundant cellular protein CypA at low drug dosage without affecting immune cells, allowing us to investigate the potential therapeutic effects associated with the endogenous protein in the future.

Context: Previous reviews of care planning (CP) interventions in care homes focus on higher quality research methodologies and exclusively consider advanced care planning (ACP), thereby excluding many intervention-based studies that could inform current practice. CP is concerned with residents’ current circumstances while ACP focuses on expressing preferences which relate to future care decisions. Objectives: To identify, map and summarise studies reporting CP interventions for older people in care homes. Methods: Seven electronic databases were searched from 1 January 2012 until 1 January 2022. Studies of CP interventions, targeted at older people (>60 years), whose primary place of residence was a care home, were eligible for inclusion. Two reviewers independently screened the titles and abstracts of 3778 articles. Following a full-text review of 404 articles, data from 112 eligible articles were extracted using a predefined data extraction form. Findings: Studies were conducted in 25 countries and the majority of studies took place in the United States, Australia and the UK. Most interventions occurred within nursing homes (61%, 68/112). More than 90% of interventions (93%, 104/112) targeted staff, and training was the most common focus (80%, 83/104), although only one included training for ancillary staff (such as cleaners and caterers). Only a third of the studies (35%, 39/112) involved family and friends, and 62% (69/112) described interventions to improve CP practices through multiple means. Limitations: Only papers written in English were included, so potentially relevant studies may have been omitted. Implications: Two groups of people – ancillary workers and family and friends – who could play a valuable role in CP were often not included in CP interventions. These oversights should be addressed in future research.

Wellcome's Institutional Fund for Research Culture (IFRC) closed call is an invite-only grant call in 2023. It is a departure from Wellcome's previous methods of institutional funding, providing institutions with up to £1m of grant funding to take on ambitious projects that advance research cultures and research environments that are equitable, diverse and supportive. Recognising the broad range of topics and ideas for advancing positive research cultures, IFRC is the first ever Wellcome-funding scheme to use partial randomisation to allocate funding. Applications were grouped by a funding committee into three categories (Gold, Silver and Bronze), with the applications selected for Gold being directly recommended for funding and all applications in the Silver group being set for funding by the randomiser. Applications grouped into Bronze were not funded. To ensure that this activity Wellcome's principles for openness and transparency, we have included the Python script for the call here. IFRC comes when efforts to fund positive and inclusive research cultures are mainstream. Similar efforts to support research culture activities at scale have come from the Research England Development (RED) Fund, and the next iteration of the Research Excellence Framework (REF 2028) will also mark 25% of the assessment criteria for people, culture and environment. IFRC was not designed with the national picture in mind but is a testament to Wellcome's values as an inclusive funder. The range of projects and geographies that IFRC will fund is exciting.Still, it also threw up several interesting social and philanthropic research questions we want to explore in future community-facing activities following the call. We hope that findings from IFRC projects become a valuable resource for institutions wishing to improve their research cultures and a catalyst for future change and discussion within the sector that makes academic careers more inclusive.

Context: In many countries, there is a specification for information that should be collected by care homes. So-called ‘minimum data-sets’ (MDS) are often lengthy, and report on resident health and wellbeing, staff, and facilities. In the UK, the absence of any easily accessible data on the care home population was highlighted at the start of the COVID-19 pandemic. Care homes faced multiple requests for data from external agencies who had little knowledge of what care homes were already collecting. Objective: This study aimed to identify the range (and method) of data collected by care home organisations, in a country without a mandated MDS. Methods: Online survey of care homes (with/without nursing) in England. Care homes recruited via research and care home networks, social media. Questions covered data content, storage, and views on data sharing, analysed with descriptive statistics. Findings: 273 responses were received, representing over 5,000 care homes. Care homes reported extensive data on the health, care and support needs of individual residents, their preferences, and activities. Clinical measures and tools adopted from health were commonly used, but few collected information on quality-of-life. Care homes reported uses of these data that included monitoring care quality, medication use, staff training needs, budgeting, and marketing. Concerns over privacy and data protection regulations are potential barriers to data sharing. Implications: These findings challenge the notion that incentives or mandates are required to stimulate data collection in care homes. Care home organisations are collecting an extensive range of resident-level information for their own uses. Countries considering introducing social care records or an MDS could start by working with care home organisations to review existing data collection and evaluate the implications of collecting and sharing data. A critical approach to the appropriateness of health-related tools in this setting is overdue.

This paper considers literary translation as a process that is both transformative and disruptive. Translation engenders movement, not only across languages, but it moves ideas from the centre to the periphery, and from the periphery to the centre. I argue that the translation of literature facilitates the movement and transfer of social narratives between languages and cultures, and in doing so, the very nature of these narratives is altered. Defining social narratives as “the stories we tell ourselves, not just those we tell other people, about the world(s) in which we live” (Baker 19), this paper considers how the properties of such narratives are transformed when translated for new audiences and readerships. Using the vocabulary of sound and volume, I identify and label social narratives on a spectrum of quiet and loud, moving away from previously used binary descriptions, in order to describe the power dynamics at play within world literature. I argue that the interaction between narratives in translation can be discussed in terms of amplification, muting, or silencing, in particular when considering the position and status of source and target languages. To demonstrate this new means with which to describe this process in translation, I take as a case study twentieth-century Catalan author Mercè Rodoreda’s novel La mort i la primavera (1986), and its English translation Death in Spring (2017), identifying how narratives interact and function across cultures, and how they may be made quieter or louder, in order to resonate with, or be ‘heard’ by new audiences.

The paper explores how postgraduate students make course selection decisions in the digital era. An exploratory study with seven postgraduate student focus groups (UK, EU and International) gained a detailed insight into this important change. The availability of information, from an increased use of digital media had a significant impact on Higher Education postgraduate decision-making. The results found a circular decision-making approach with evidence of rational and emotional decisions where students do not always commence with a wide choice set. Online forums, Word-of-Mouth/electronic Word-of-Mouth from past/existing students, family and friends are important influencers, as students considered postgraduate study from one month to four years prior to starting a course. We identified 5 different application pattern categories, together with highlighting the importance of evaluating the students' pre-purchase experience during the application process. The research highlights the need for universities to continually engage during the decision-making process and to evaluate pre-purchase experiences.

IntroductionMany Aboriginal and Torres Strait Islander people living on Kaurna Country in northern Adelaide experience adverse health and social circumstances. The Taingiwilta Pirku Kawantila study sought to understand challenges facing Aboriginal and Torres Strait Islander communities and identify solutions for the health and social service system to promote social and emotional wellbeing.MethodsThis qualitative study applied Indigenous methodologies undertaken with Aboriginal and Torres Strait Islander governance and leadership. A respected local Aboriginal person engaged with Aboriginal and Torres Strait Islander community members and service providers through semi-structured interviews and yarning circles that explored community needs and challenges, service gaps, access barriers, success stories, proposed strategies to address service and system challenges, and principles and values for service design. A content analysis identified the breadth of challenges in addition to describing key targets to empower and connect communities and optimize health and social services to strengthen individual and collective social and emotional wellbeing.ResultsEighty-three participants contributed to interviews and yarning circles including 17 Aboriginal community members, 38 Aboriginal and Torres Strait Islander service providers, and 28 non-Indigenous service providers. They expressed the need for codesigned, strengths-based, accessible and flexible services delivered by Aboriginal and Torres Strait Islander workers with lived experience employed in organisations with Aboriginal and Torres Strait Islander leadership and governance. Community hubs and cultural events in addition to one-stop-shop service centres and pre-crisis mental health, drug and alcohol and homelessness services were among many strategies identified.ConclusionHolistic approaches to the promotion of social and emotional wellbeing are critical. Aboriginal and Torres Strait Islander people are calling for places in the community to connect and practice culture. They seek culturally safe systems that enable equitable access to and navigation of health and social services. Aboriginal and Torres Strait Islander workforce leading engagement with clients is seen to safeguard against judgement and discrimination, rebuild community trust in the service system and promote streamlined access to crucial services.

Background: Efforts to build and foster adult social care research in England have historically encountered more challenges to its growth and expansion compared with health research, with a sector facing significant barriers in facilitating research activity due to a lack of resourcing, poor valuation or understanding of the profile of social care research. The landscape for supporting research in adult social care has been rather bleak, but in recent years there has been recognition of the need to foster a research community. The National Institute for Health and Care Research in England have committed to investing in social care research capacity by funding six adult social care partnerships, with one based in Southeast England. Process developing Communities of Practice (COPs): Three large online networking events were held in the first year of the project to engage managers and practitioners from the local authority and from the wider adult social care sector. These took place in July and November 2021, with a last event in March 2022. Two COPs were identified, following an ordering and thematising process of feedback from the networking events, of: (a) Supporting people with complex needs throughout the lifespan, and (b) Enhancing, diversifying and sustaining the social care workforce. Whilst it would be premature to identify their long-term impacts, through the facilitation of 20 COP meetings held so far, alongside the engagement platforms and enrichment resources, these have provided a space for regular communication in the sector, knowledge sharing and networking between COP members. Conclusion: The COP framework offers a collaborative approach to initiating research from the grass-roots level in adult social care. This paper focuses on how the COP model offers great promise for knowledge-exchange providing a forum to generate and disseminate knowledge around social care in our two COP domains.

A hallmark of cocaine use disorder (CUD) is dysfunction of dopamine signaling in the mesolimbic pathway, including impaired dopamine 2 (D2) receptor signaling. One of the most replicated findings in human imagining studies is decreased striatal D2 receptor binding in individuals with a substance use disorder relative to healthy controls; however, the vast majority of the data is from males, and findings in smokers suggest this molecular shift may not translate to females. The goal of this study was to determine whether there are sex differences in the role of D2 receptors in motivating cocaine use prior to and following the development of an addiction-like phenotype (defined by an enhanced motivation for cocaine relative to the short-access, ShA, group). Here, male and female rats were given ShA (20 infusions/day, 3 days) or extended-access (ExA; 24h/day, 96 infusions/day, 10 days) to cocaine self-administration and then following 14 days of withdrawal, were tested under a progressive-ratio schedule to assess motivation for cocaine use. Once a stable level of motivation was established, the effect of NAc-infusions of the D2 receptor antagonist eticlopride (0–3.0 µg/side) were examined. We found that in males, eticlopride was less effective at decreasing motivation for cocaine following ExA versus ShA self-administration, particularly at low eticlopride doses. In contrast, in females, there were no differences in the effectiveness of eticlopride between ExA and ShA. These findings indicate that males, but not females, become less sensitive to NAc-D2 receptor antagonism with the development of an addiction-like phenotype.

Background: Certain procedures, particularly those used to treat symptoms of bladder pain syndrome/interstitial cystitis (BPS/IC), involve filling the bladder to or over its capacity for visualization and/or relief of symptoms. Rarely, if excessive pressure or volume is used, bladders may rupture causing significant harm to the patient. The purpose of this study was to identify baseline data for pressure and volume when hydrodistention is attempted in explanted cadaveric bladders, as well as determine bladder rupture pressure changes in the acute post-cystorrhaphy state. Methods: Eight explanted cadaveric bladders were filled using a systematic digital pump system. Intravesical pressure and volume were monitored during the filling phase until rupture. A two-layer cystorrhaphy was performed followed by bladder refilling to point of rupture. The pressure-volume correlations were developed for the explanted bladders, pre and post rupture. Results: The mean intact bladder rupture volume was 1186.3 mL ± 356.1 (range 450.0–1550.0) and mean pressure of 103.4 cm H2O ± 45.9 (range 59.0–190.0). The mean bladder rupture volume following repair was 1051.9 mL ± 251.3 (range 500.0–1300.0) while the mean pressure dropped to 53.1 cm H2O ± 44.0 (range 18.0–149.0). Compliance was noted to decrease significantly with a 54% drop in maximal pressure immediately prior to repeat rupture. Location of the initial rupture site did not have an impact on volume or pressures achieved. The weakest point post-cystorrhaphy consistently involved the original cystotomy site. Conclusions: This study provides ex-vivo bladder parameters that may guide providers in distention and post-rupture cases. Repeat rupture pressure (maximal bladder pressure achieved) and bladder compliance were noted to be significantly lower immediately post-cystorrhaphy.

Understanding mosquito interaction with long-lasting insecticidal bednets is crucial in the development of more effective intervention methods to protect humans from malaria transmission. As such, a 240 × 240 × 1000 mm laboratory setup for the in-line recording of digital holograms and subsequent in-focus reconstruction and 3D localisation of mosquitoes is presented. Simple bednet background removal methods are used to accurately localise a mosquito obscured by a bednet in 3D coordinates. Simulations and physical data demonstrate that this method is suitable for mosquitoes positioned 3−1000 mm behind a bednet. A novel post-processing technique, involving a cascade-correlation of a Tamura of Intensity focus metric extracted from digitally reconstructed scenes, accurately localises mosquitoes positioned 35−100 mm behind a bednet from a single digital hologram. The result of this study is a scalable digital holographic methodology to examine mosquito-bednet interaction in 3D at a level of accuracy previously only seen in 2D imaging of mosquitoes in a much smaller volume.

Abstract Background It is important to involve older people in evaluating public programmes that affect their lives. This includes those with physical and cognitive impairments (such as dementia) who may need support to live at home. Many countries have implemented new approaches to support older people to live well at home for longer. However, it can be challenging to involve disabled people in service evaluation, so we are unclear whether services are meeting their needs. Aim This study explored how a cascading methodology, offering different supports enabled the involvement of home care users with cognitive and physical impairments in the assessment of their care‐related quality of life. Method We used multiple tools from the Adult Social Care Outcomes Toolkit (ASCOT) with n = 63 older adults who were recipients of home care in the Illawarra. We also offered different physical and cognitive supports as needed. Results We started with the standard ASCOT questionnaire to assess the care‐related quality of life, but then offered alternative formats (including Easy Read) and supports (including physical and cognitive assistance) if the older person needed them to participate. This allowed us to involve a greater diversity of older people in the evaluation, and changed what we found out about whether their care needs were being met. Conclusion There is a need to implement more flexible and inclusive methods to increase the involvement of vulnerable users of long‐term care in the assessment of service outcomes. This is important to ensure that the perspectives of all service users inform the delivery of person‐centred care. It is also critical to understand the extent to which programmes are meeting the needs of vulnerable service users. Patient or Public Contribution Service users with dementia were involved in the design of the ‘Easy Read’ questionnaire used in the study.

Child-centred disaster risk reduction and climate change adaptation have gained traction through projects and programs implemented by various actors worldwide. However, there remains a lack of understanding of their longer-term impact and influence on policy and practice at different levels of governance. This longitudinal research examines the processes of mainstreaming child-centred disaster risk reduction (DRR) and school safety programs at various levels. The data collection methods included participatory workshops, focus group discussions, and participant observations collected in 2008 and 2019. The findings suggest that the existence of local disaster regulation and mainstream institutions does not serve as a legitimate predictor for how likely governments adopt child-centred DRR and sustain school safety policy implementation. By adopting hybrid and combining approaches to DRR institutionalisation, NGOs and governments have collaboratively combined various strategies, including local regulatory change, incentives, nudging, and coercive and discursive approaches.

Informed by the ideology of 'deliverology', performance measurement has become a core component of how English schools are held accountable for the quality of their provision. A wealth of research conducted in diverse national contexts where this approach has been influential has suggested that the unintended harms it generates -- including a widening of inequalities, a test-driven pedagogic culture and a narrowing of the curriculum -- may be outweighing its benefits. In an attempt to circumnavigate such perverse effects, the performance measures used in England have become increasingly sophisticated in recent years, giving them a "prima facie" plausibility that has led to them being welcomed by some progressive educators as a means of increasing access to high-status knowledge for disadvantaged students. This paper uses data from a survey of English school teachers to interrogate this plausibility. The analysis suggests that when we drill down into the daily life of schools and its underlying logic it becomes increasingly difficult to be comfortable with the progressive defence of the performance measures currently in use; and that, far from improving educational quality, the measures themselves, and the wider deliverology framework with which they are associated, are in certain fundamental respects incompatible with quality improvement.

Purpose/objectives: The aim of this study was to quantitatively investigate the impact of stereoscopic three‐dimensional (3D) vision on students' performance when compared with that of two‐dimensional (2D) vision in a 3D virtual reality (VR) simulator. Methods: Twenty‐four dental students (second‐ and fourth‐year BDS) were assigned to perform three operative tasks under 3D and 2D viewing conditions on a Virteasy (HRV) simulator. Groups were crossed over and all students performed the same tasks under the alternate viewing conditions. The performance was evaluated by (1) accuracy, (2) outside target area removal, and (3) tooth cutting time, automatically using the generated feedback. Results: Twenty‐one participants completed all sessions. The results revealed a statistically significant effect of 3D vision over 2D vision on students' performance in terms of accuracy (p = 0.035). Stereoscopic 3D vision showed significant effect on outside target area removal in the first task (p = 0.035). Tooth cutting time was the same under both conditions (p = 0.766). The findings revealed improvement in accuracy score and reduction in outside target area removal over the course of the experiment under both conditions. Comparing the difference in 3D effect in the early and advanced learning groups revealed no significant difference among the groups (p > 0.05). Conclusion: Utilizing stereoscopic 3D vision in the training session improved students' perception of depth which led to more accurate tooth cutting within the target area, and less outside target area removal. However, 3D shows a limited impact on task completion time. [ABSTRACT FROM AUTHOR]

The stochastic nature of environmental factors that govern the behavior of fire, such as wind and fuel, exposes wildfire modeling to a degree of uncertainty. In order to produce more realistic wildfire predictions, it is, therefore, necessary to incorporate these uncertainties within wildfire models in a way that reflects the influence of environmental stochasticity on wildfire propagation. Otherwise, the risks of the potential danger of a given wildfire may be under-represented. Specifically, environmental stochasticity in the form of wind variability results in considerable uncertainty in the output of fire spread models. Here, we consider two stochastic wind models and their implementation in the spark fire simulator framework to capture the environmental uncertainty related to wind variability. The results are compared with the output from purely deterministic wildfire spread models and are discussed in the context of the potential ramifications for wildfire risk management.

We examine the relationship between how teachers talk about teaching and their actual teaching practices. Analyses of their talk were based on extensive transcripts and writings and focused on metaphors and images invoked when discussing knowledge, learning, and teaching. Three distinct and coherent webs of association were identified, which we describe as "traditional," "reform," and "middling." For both traditional and reform teachers, preferred webs of association proved to be highly consistent with classroom practices. For teachers who tended to draw on the "middling" web, practices tended to vary dramatically, and habits of speaking appeared to be linked to frustrations with teaching. Implications for professional learning are discussed.

Background: The ASCOT-ER is an adapted easy-read version of the ASCOT-SCT4, a self-report measure of social care-related quality of life (SCRQoL) for social care evaluation. In this study, we investigated the instrument's feasibility, construct validity and factor structure. Method: Data were collected from 264 service users in England. Feasibility was evaluated by missing data and help to complete the questionnaire. Scale dimensionality was assessed using exploratory factor analysis. Construct validity was evaluated by hypothesis testing. Results: Convergent validity was supported by moderate to strong correlations between ASCOT-ER and personal wellbeing and overall quality of life, as well as with individual characteristics. Exploratory factor analysis indicated that the ASCOT-ER is a unidimensional scale. Low missingness indicates that the instrument is feasible; however, most respondents needed some level of support to complete the questionnaire. Conclusion: The study provides preliminary evidence of the ASCOT-ER's feasibility, unidimensionality and construct validity.

Academics without PhDs are common in developing countries and among lecturers from marginalised communities, yet the literature on doctoral education largely ignores them. This qualitative study aimed to address that gap by interviewing academics without PhDs in South Africa and Australia. Their narratives of betwixt and betweenness contribute to theories of liminality as well as doctoral education. Liminality is traditionally conceptualised as a linear, vertical process with clear rites of passage. However, in our study, the interviewees were not only facing a vertical trajectory between non-PhD and post-PhD status but also a lateral trajectory between staff and student identity. The research confirms the importance of distinguishing between transient and permanent liminality in an occupational context. For those who had given up studying, liminality was permanent. Liminality was also affected by dynamically interconnecting factors including age, gender, race, ethnicity, relations with supervisors, time and location.

Dynamic assessment (DA) is appealing to educational psychologists (EPs) due to: its flexibility, allowing EPs to adjust materials and processes to fit the assessment context; its usefulness, revealing ideas about how the next steps for learning might be achieved; and its focus on strengths. In Feuerstein's words, "it is the instances of success of the individual that are the focal point for analysis for the reasons of success and failure". Given the appeal of DA, it is frustrating that it has not been taken up more by practitioners. This paper will explore what DA is, and what it is not, summarise its advantages, consider why it is not more widely used, and introduce one way in which EPs can receive support for DA; using video of an EP "doing" DA within supervision in order to reflect on "good" DA.

Grouping pupils by attainment is frequently practised in primary schools yet is associated with detrimental effects for middle- and lower-attaining children. Drawing on a mixed methods study, we find that attainment grouping practices at key stage 2 in primary schools are seldom straightforward. Although grouping by attainment appears to be the dominant form of grouping, the language used by teachers to talk about their classroom practice suggests a varied and sometimes complex picture. We explore how school leaders and teachers justify their grouping practices and conclude that primary school educators endeavour to strike a balance between their concern for the child and the need to respond to the demands of testing and assessment. In the wake of new reforms to primary education, the findings in this study are significant and timely in providing a picture of the types of grouping currently being carried out in primary schools across England.

This paper returns to a long-standing theme in education research, the ways in which 'contextual factors impact on what schools do, as well as directly on what pupils achieve' (Lupton, 2004, 4). Drawing on a project designed to explore the early effects of reforms to national examinations, the curriculum for 14-16 year olds and school accountability measures in English secondary schools, this paper considers the perceptions and experiences of teachers currently charged with enacting these reforms specifically in the light of their situated school realities in three different settings. A case is made for a contextually sensitive approach towards policy making and policy enactment that takes account of some of the more nuanced distinctions among schools' contextual positionings.

Conservativism has gained significant influence on education-policy making and debates about education in many Anglophone countries. While conservative educational governments have advanced some neoliberal governance trends, they have also introduced characteristic neoconservative education elements, notably in the area of curricular content. This article focuses on the impact of conservative ideology on curriculum and assessment policies in English secondary education and specifically explores schools' first reactions to the introduction of a policy initiative that is emblematic of neoconservatism, the English Baccalaureate. The empirical discussion relies on a mixed methods study on the reception of the latest assessment and curriculum policies in English secondary schools. The findings suggest that the current reforms are transforming school subject hierarchies, resource allocation across subjects, and what counts as knowledge in English secondary schools, and introducing a new culture of subject--and by implication, teacher and student--'worth'.

Abstract Background Since the novel coronavirus SARS-COV-2 was first identified to be circulating in the US on January 20, 2020, some of the worst outbreaks have occurred within state and federal prisons. The vulnerability of incarcerated populations, and the additional threats posed to the health of prison staff and the people they contact in surrounding communities underline the need to better understand the dynamics of transmission in the inter-linked incarcerated population/staff/community sub-populations to better inform optimal control of SARS-COV-2. Methods We examined SARS-CoV-2 case data from 101 non-administrative federal prisons between 5/18/2020 to 01/31/2021 and examined the per capita size of outbreaks in staff and the incarcerated population compared to outbreaks in the communities in the counties surrounding the prisons during the summer and winter waves of the SARS-COV-2 pandemic. We also examined the impact of decarceration on per capita rates in the staff/incarcerated/community populations. Results For both the summer and winter waves we found significant inter-correlations between per capita rates in the outbreaks among the incarcerated population, staff, and the community. Over-all during the pandemic, per capita rates were significantly higher in the incarcerated population than in both the staff and community (paired Student’s t-test p = 0.03 and p

Abstract Cell cycle associated protein 1 (Caprin1) is an RNA-binding protein that can regulate the cellular post-transcriptional response to stress. It is a component of both stress granules and neuronal RNA granules and is implicated in neurodegenerative disease, synaptic plasticity and long-term memory formation. Our previous work suggested that Caprin1 also plays a role in the response of the cochlea to stress. Here, targeted inner ear-deletion of Caprin1 in mice leads to an early onset, progressive hearing loss. Auditory brainstem responses from Caprin1-deficient mice show reduced thresholds, with a significant reduction in wave-I amplitudes compared to wildtype. Whilst hair cell structure and numbers were normal, the inner hair cell-spiral ganglion neuron (IHC-SGN) synapse revealed abnormally large post-synaptic GluA2 receptor puncta, a defect consistent with the observed wave-I reduction. Unlike wildtype mice, mild-noise-induced hearing threshold shifts in Caprin1-deficient mice did not recover. Oxidative stress triggered TIA-1/HuR-positive stress granule formation in ex-vivo cochlear explants from Caprin1-deficient mice, showing that stress granules could still be induced. Taken together, these findings suggest that Caprin1 plays a key role in maintenance of auditory function, where it regulates the normal status of the IHC-SGN synapse.

Abstract Background Care homes provide long term care for older people. Countries with standardised approaches to residents’ assessment, care planning and review (known as minimum data sets (MDS)) use the aggregate data to guide resource allocation, monitor quality, and for research. Less is known about how an MDS affects how staff assess, provide and review residents’ everyday care. The review aimed to develop a theory-driven understanding of how care home staff can effectively implement and use MDS to plan and deliver care for residents. Methods The realist review was organised according to RAMESES (Realist And Meta-narrative Evidence Synthesis: and Evolving Standards) guidelines. There were three overlapping stages: 1) defining the scope of the review and theory development on the use of minimum data set 2) testing and refining candidate programme theories through iterative literature searches and stakeholders’ consultations as well as discussion among the research team; and 3) data synthesis from stages 1 and 2. The following databases were used MEDLINE via OVID, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), ASSIA [Applied Social Sciences Citation Index and Abstracts]) and sources of grey literature. Results Fifty-one papers informed the development of three key interlinked theoretical propositions: motivation (mandates and incentives for Minimum Data Set completion); frontline staff monitoring (when Minimum Data Set completion is built into the working practices of the care home); and embedded recording systems (Minimum Data Set recording system is integral to collecting residents’ data). By valuing the contributions of staff and building on existing ways of working, the uptake and use of an MDS could enable all staff to learn with and from each other about what is important for residents’ care Conclusions Minimum Data Sets provides commissioners service providers and researchers with standardised information useful for commissioning planning and analysis. For it to be equally useful for care home staff it requires key activities that address the staff experiences of care, their work with others and the use of digital technology. Registration PROSPERO registration number CRD42020171323.

Abstract Background The NF-κB family of transcription factors and associated signalling pathways are abundant and ubiquitous in human immune responses. Activation of NF-κB transcription factors by viral pathogen-associated molecular patterns, such as viral RNA and DNA, is fundamental to anti-viral innate immune defences and pro-inflammatory cytokine production that steers adaptive immune responses. Diverse non-viral stimuli, such as lipopolysaccharide and cytokines, also activate NF-κB and the same anti-pathogen gene networks. Viruses adapted to human cells often encode multiple proteins targeting the NF-κB pathway to mitigate the anti-viral effects of NF-κB-dependent host immunity. Results In this study we have demonstrated using a variety of assays, in a number of different cell types including primary cells, that plasmid-encoded or virus-delivered simian immunodeficiency virus (SIV) accessory protein Vpx is a broad antagonist of NF-κB signalling active against diverse innate NF-κB agonists. Using targeted Vpx mutagenesis, we showed that this novel Vpx phenotype is independent of known Vpx cofactor DCAF1 and other cellular binding partners, including SAMHD1, STING and the HUSH complex. We found that Vpx co-immunoprecipitated with canonical NF-κB transcription factor p65, but not NF-κB family members p50 or p100, preventing nuclear translocation of p65. We found that broad antagonism of NF-κB activation by Vpx was conserved across distantly related lentiviruses as well as for Vpr from SIV Mona monkey (SIVmon), which has Vpx-like SAMHD1-degradation activity. Conclusions We have discovered a novel mechanism by which lentiviruses antagonise NF-κB activation by targeting p65. These findings extend our knowledge of how lentiviruses manipulate universal regulators of immunity to avoid the anti-viral sequelae of pro-inflammatory gene expression stimulated by both viral and extra-viral agonists. Importantly our findings are also relevant to the gene therapy field where virus-like particle associated Vpx is routinely used to enhance vector transduction through antagonism of SAMHD1, and perhaps also through manipulation of NF-κB. Graphical Abstract

Background: Measurement models inform the approach to assess a measure’s validity and also how a measure is understood, applied and interpreted. With preference-based measures, it is generally accepted that they are formative; however, if they are applied without preferences, they may be reflective, formative or mixed. In this study, we sought to empirically test whether the reflective, formative or mixed measurement model best describes PBMs of social care-related quality of life (ASCOT, ASCOT-Carer). We also explored the network approach, as an alternative. Methods: ASCOT and ASCOT-Carer data were analyzed using confirmatory factor analysis and Multiple Indicators Multiple Causes models to test reflective, formative or mixed measurement models, respectively. Network analysis of partial correlations using the Gaussian graphical model was also conducted. Results: The results indicated that the reflective measurement model is the worst fit for ASCOT and ASCOT-Carer. The formative or mixed models may apply to ASCOT. The mixed model was the best fit for ASCOT-Carer. The network analysis indicated that the most important or influential items were Occupation and Personal cleanliness and comfort (ASCOT) and Time and space and Self-care (ASCOT-Carer). Conclusions: The ASCOT and ASCOT-Carer are best described as formative/mixed or mixed models, respectively. These findings may guide the approach to the validation of cross-culturally adapted and translated versions. Specifically, we recommend that EFA be applied to establish structural characteristics, especially if the measure will be applied as a PBM and as a measure of SCRQoL. Network analysis may also provide further useful insights into structural characteristics.

Introduction Health and care data are routinely collected about care home residents in England, yet there is no way to collate these data to inform benchmarking and improvement. The Developing research resources And minimum data set for Care Homes’ Adoption and use study has developed a prototype minimum data set (MDS) for piloting.Methods and analysis A mixed-methods longitudinal pilot study will be conducted in 60 care homes (approximately 960 residents) in 3 regions of England, using resident data from cloud-based digital care home records at two-time points. These will be linked to resident and care home level data held within routine National Health Service and social care data sets. Two rounds of focus groups with care home staff (n=8–10 per region) and additional interviews with external stakeholders (n=3 per region) will explore implementation and the perceived utility of the MDS. Data will be assessed for completeness and timeliness of completion. Descriptive statistics, including percentage floor and ceiling effects, will establish data quality. For validated scales, construct validity will be assessed by hypothesis testing and exploratory factor analysis will establish structural validity. Internal consistency will be established using Cronbach’s alpha. Longitudinal analysis of the pilot data will demonstrate the value of the MDS to each region. Qualitative data will be analysed inductively using thematic analysis to understand the complexities of implementing an MDS in care homes for older people.Ethics and dissemination The study has received ethical approval from the London Queen’s Square Research Ethics Committee (22/LO/0250). Informed consent is required for participation. Findings will be disseminated to: academics working on data use and integration in social care, care sector organisations, policy makers and commissioners. Findings will be published in peer-reviewed journals. Partner NIHR Applied Research Collaborations, the National Care Forum and the British Geriatrics Society will disseminate policy briefs.

The tuberal hypothalamus controls life-supporting homeostatic processes, but despite its fundamental role, the cells and signalling pathways that specify this unique region of the central nervous system in embryogenesis are poorly characterised. Here, we combine experimental and bioinformatic approaches in the embryonic chick to show that the tuberal hypothalamus is progressively generated from hypothalamic floor plate-like cells. Fate-mapping studies show that a stream of tuberal progenitors develops in the anterior-ventral neural tube as a wave of neuroepithelial-derived BMP signalling sweeps from anterior to posterior through the hypothalamic floor plate. As later-specified posterior tuberal progenitors are generated, early specified anterior tuberal progenitors become progressively more distant from these BMP signals and differentiate into tuberal neurogenic cells. Gain- and loss-of-function experiments in vivo and ex vivo show that BMP signalling initiates tuberal progenitor specification, but must be eliminated for these to progress to anterior neurogenic progenitors. scRNA-Seq profiling shows that tuberal progenitors that are specified after the major period of anterior tuberal specification begin to upregulate genes that characterise radial glial cells. This study provides an integrated account of the development of the tuberal hypothalamus.

IntroductionWomen have a shorter course from initial cocaine use to meeting the criteria for cocaine use disorder as compared to men. Preclinical findings similarly indicate that females develop key features of an addiction-like phenotype faster than males, including an enhanced motivation for cocaine and compulsive use, indicating that this phenomenon is biologically based. The goals of this study were to determine whether cocaine-craving, another key feature of addiction, also develops sooner during withdrawal in females than males and to determine whether there are sex differences in the molecular mechanisms associated with its development focusing on markers known to mediate cocaine-craving in males (i.e., dorsomedial prefrontal cortex, dmPFC, expression of brain-derived neurotrophic factor exon-IV, Bdnf-IV, and NMDA receptor subunits, Grin2a, Grin2b, and Grin1).MethodsCocaine-craving was assessed following extended-access cocaine self-administration and 2, 7, or 14 days of withdrawal using an extinction/cue-induced reinstatement procedure. Tissue was obtained from the dmPFC immediately after reinstatement testing and gene expression changes were analyzed using real-time qPCR.ResultsIn males, cocaine-craving (total extinction and cue-induced reinstatement responding) progressively increased from early to later withdrawal time-points whereas in females, cocaine-craving was already elevated during early withdrawal (after 2 days) and did not further increase at later withdrawal time-points. Levels of cocaine-craving, however, were similar between the sexes. Gene expression changes differed markedly between the sexes such that males showed the expected relapse- and withdrawal-associated changes in Bdnf-IV, Grin2a, Grin2b, and Grin1 expression, but females only showed a modest increase Grin1 expression at the intermediate withdrawal timepoint.DiscussionThese findings indicate that cocaine-craving is similarly expressed in males and females although the time-course for its incubation appears to be accelerated in females; the molecular mechanisms also likely differ in females versus males.