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Background There is growing evidence that exposure to unhealthy urban environments increases the risk of developing non-communicable diseases (e.g. diabetes, cardiovascular disease, and respiratory illness), with marginalised communities bearing the greatest burden. However, to date, evidence alone has not been sufficient to make health a top priority in the development of urban environments. Methods The aim of this study was to develop and optimise an intervention to increase the intention to act on health and health inequalities by private sector professionals working in urban development, with a focus on consultants and developers. The ‘Changing Mindsets’ intervention was developed through an iterative co-production process using the Person-Based Approach method, drawing on evidence and a novel theoretical framework. Results Intervention development consisted of three stages. Stage 1 involved the collation of theory and evidence, which included the development of a novel theoretical framework, primary mixed methods research and stakeholder engagement. Stage 2 was the intervention modelling phase, where the findings from Stage 1 were integrated through the guiding principles and behavioural analysis tables, which informed the logic model. Stage 3 involved iterative intervention optimisation with members of the target population. The intervention was comprised of two elements: 1) An intervention session consisting of a presentation with group discussion presented by one of the two industry partners working in the private sector of urban development, and 2) A website signposting to tools and resources, networks to support prioritising and integrating health into urban development, and examples of how other organisations have done so. Conclusions We have provided insights into how complex interdisciplinary theory can be combined with evidence of the target group’s needs, issues and challenges using established methodology from the Person-Based Approach and behavioural science. Changing Mindsets is currently being evaluated for its effectiveness and acceptability in the target population. Subsequent to this, there are plans to adapt the intervention to increase the intention to act on other social issues and for other populations. Trial registration ISRCTN12310546 registered on the 30 th March 2021.

The variety of those projects is important and includes 275,000 sq ft of grade-A office space, 92,000 sq ft of flexible creative office space, a hotel and BTR and affordable housing residential schemes. Working closely with the council, Dandara was one developer that secured planning committee approval during 2020 - a BTR and affordable housing scheme and the first for the Bedminster Green regeneration area, giving it that important kick-start. Other permissions included a new library and a new campus for the University of Bristol, an arena, a new harbourside tourist attraction and a mixed-use scheme of residential, student, offices and a school as part of the St Philip's Marsh regeneration area.

A Smile Split by the Stars: An Experiment by Katherine McKittrick with т. nourbeSe philip, Muna Dahir, Roya DelSol, Cora Gilroy-Ware, Nasrin Himada, Yaniya Lee, Sameen Mahboubi, Juliane Okot Bitek, Cristian Ordóñez, Trish Salah, Chloé Savoie-Bernard, Aaliyah Strachan Gallery 44 Centre for Contemporary Photography, Toronto, 4 April to 24 May 2025 by Zoe Imani Sharpe Lately I've found myself asking: what is poetry doing in art galleries and museums? I believe poetry, at its best, is alive, and that, perhaps, we should be critical or weary of any institutional framework that attempts to stifle, objectify, or master its (potentially insurgent) energies. [...]the girls focus on declension-a linguistic term that explains how a words form changes to express its syntactic role in a sentence -articulates itself through shifting address, irresolution, and conditional negations. An exhibition text comes in the form of a conversation-response between Kai Trotz-Motayne and Erica N. Cardwell, alongside an essay by Muna Dahir, an essay-book by McKittrick, and an index-interview between philip and Yaniya Lee.

Current inflammatory bowel disease (IBD) therapies are ineffective in a high proportion of patients. Combining bulk and single-cell transcriptomics, quantitative histopathology and in situ localization across three cohorts of patients with IBD (total n  = 376), we identify coexpressed gene modules within the heterogeneous tissular inflammatory response in IBD that map to distinct histopathological and cellular features (pathotypes). One of these pathotypes is defined by high neutrophil infiltration, activation of fibroblasts and vascular remodeling at sites of deep ulceration. Activated fibroblasts in the ulcer bed display neutrophil-chemoattractant properties that are IL-1R, but not TNF, dependent. Pathotype-associated neutrophil and fibroblast signatures are increased in nonresponders to several therapies across four independent cohorts (total n  = 343). The identification of distinct, localized, tissular pathotypes will aid precision targeting of current therapeutics and provides a biological rationale for IL-1 signaling blockade in ulcerating disease. Transcriptomic and histological profiling of gut biopsies from multiple independent cohorts of patients with inflammatory bowel disease identifies distinct histopathological, molecular and cellular features associated with treatment response, providing insights for patient stratification and precision therapy.

Objective: State-issued behavioral policy interventions (BPIs) can limit community spread of COVID-19, but their effects on COVID-19 transmission may vary by level of social vulnerability in the community. We examined the association between the duration of BPIs and the incidence of COVID-19 across levels of social vulnerability in US counties. Methods: We used COVID-19 case counts from USAFacts and policy data on BPIs (face mask mandates, stay-at-home orders, gathering bans) in place from April through December 2020 and the 2018 Social Vulnerability Index (SVI) from the Centers for Disease Control and Prevention. We conducted multilevel linear regression to estimate the associations between duration of each BPI and monthly incidence of COVID-19 (cases per 100 000 population) by SVI quartiles (grouped as low, moderate low, moderate high, and high social vulnerability) for 3141 US counties. Results: Having a BPI in place for longer durations (ie, ≥2 months) was associated with lower incidence of COVID-19 compared with having a BPI in place for <1 month. Compared with having no BPI in place or a BPI in place for <1 month, differences in marginal mean monthly incidence of COVID-19 per 100 000 population for a BPI in place for ≥2 months ranged from –4 cases in counties with low SVI to –401 cases in counties with high SVI for face mask mandates, from –31 cases in counties with low SVI to –208 cases in counties with high SVI for stay-at-home orders, and from –227 cases in counties with low SVI to –628 cases in counties with high SVI for gathering bans. Conclusions: Establishing COVID-19 prevention measures for longer durations may help reduce COVID-19 transmission, especially in communities with high levels of social vulnerability.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18–55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 1010 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606. Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493–1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96–317; n=127), and were boosted following a second dose (639 EU, 360–792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001). ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 programme. UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and the German Center for Infection Research (DZIF), Partner site Gießen-Marburg-Langen.

DNA content and cell volume have both been hypothesized as controls on metabolic rate and other physiological traits. We use cultures of two cryptic species of Ditylum brightwellii (West) Grunow with an approximately two-fold difference in genome size and a small and large culture of each clone obtained by isolating small and large cells to compare the physiological consequences of size changes due to differences in DNA content and reduction in cell size following many generations of asexual reproduction. We quantified the growth rate, the functional absorption cross-section of photosystem II (PSII), susceptibility of PSII to photoinactivation, PSII repair capacity, and PSII reaction center proteins D1 (PsbA) and D2 (PsbD) for each culture at a range of irradiances. The species with the smaller genome has a higher growth rate and, when acclimated to growth-limiting irradiance, has higher PSII repair rate capacity, PSII functional optical absorption cross-section, and PsbA per unit protein, relative to the species with the larger genome. By contrast, cell division rates vary little within clonal cultures of the same species despite significant differences in average cell volume. Given the similarity in cell division rates within species, larger cells within species have a higher demand for biosynthetic reductant. As a consequence, larger cells within species have higher numbers of PSII per unit protein (PsbA), since PSII photochemically generates the reductant to support biosynthesis. These results suggest that DNA content, as opposed to cell volume, has a key role in setting the differences in maximum growth rate across diatom species of different size while PSII content and related photophysiological traits are influenced by both growth rate and cell size.

Background As COVID-19 spread across the globe, cancer services were required to rapidly pivot to minimise risks without compromising outcomes for patients or staff. The aim of this study was to document changes to oncology services as a result of COVID-19 from the perspectives of both providers and receivers of care during the initial phase of the pandemic. Methods Participants were recruited between June and December 2020 through an email invitation via professional or consumer organisations, two hospital-based oncology services and snowballing. Semi-structured interviews focused on health service changes and their impacts, which were then analysed by thematic analysis. Results Thirty-two patients, 16 carers and 29 health professionals were recruited. Fifteen patients ( n = 47%) had localised disease, and 19 ( n = 59%) were currently receiving treatment. Oncology staff included oncologists, palliative care physicians, nurses, allied health and psychosocial practitioners. Four themes arose from the data: safety, increased stress and burnout, communication challenges and quality of cancer care. Conclusions There is an ongoing need for cancer-specific information from a single, trusted source to inform medical practitioners and patients/carers. More data are required to inform evidence-based guidelines for cancer care during future pandemics. All stakeholders require ongoing support to avoid stress and burnout.

Timing of organ development during embryogenesis is coordinated such that at birth, organ and fetal size and maturity are appropriately proportioned. The extent to which local developmental timers are integrated with each other and with the signaling interactions that regulate morphogenesis to achieve this end is not understood. Using the absolute requirement for a signaling pathway activity (bone morphogenetic protein, BMP) during a critical stage of tooth development, we show that suboptimal levels of BMP signaling do not lead to abnormal morphogenesis, as suggested by mutants affecting BMP signaling, but to a 24-h stalling of the intrinsic developmental clock of the tooth. During this time, BMP levels accumulate to reach critical levels whereupon tooth development restarts, accelerates to catch up with development of the rest of the embryo and completes normal morphogenesis. This suggests that individual organs can autonomously control their developmental timing to adjust their stage of development to that of other organs. We also find that although BMP signaling is critical for the bud-to-cap transition in all teeth, levels of BMP signaling are regulated differently in multicusped teeth. We identify an interaction between two homeodomain transcription factors, Barx1 and Msx1, which is responsible for setting critical levels of BMP activity in multicusped teeth and provides evidence that correlates the levels of Barx1 transcriptional activity with cuspal complexity. This study highlights the importance of absolute levels of signaling activity for development and illustrates remarkable self-regulation in organogenesis that ensures coordination of developmental processes such that timing is subordinate to developmental structure.

Gene repression is crucial to the maintenance of differentiated cell types in multicellular organisms, whereas aberrant silencing can lead to disease. The organization of DNA into chromatin and heterochromatin 1 is implicated in gene silencing. In chromatin, DNA wraps around histones, creating nucleosomes. Further condensation of chromatin, associated with large blocks of repetitive DNA sequences, is known as heterochromatin. Position effect variegation (PEV) occurs when a gene is located abnormally close to heterochromatin, silencing the affected gene in a proportion of cells 1 . Here we show that the relatively short triplet-repeat expansions found in myotonic dystrophy and Friedreich's ataxia confer variegation of expression on a linked transgene in mice. Silencing was correlated with a decrease in promoter accessibility and was enhanced by the classical PEV modifier heterochromatin protein 1 (HP1). Notably, triplet-repeat-associated variegation was not restricted to classical heterochromatic regions but occurred irrespective of chromosomal location. Because the phenomenon described here shares important features with PEV, the mechanisms underlying heterochromatin-mediated silencing might have a role in gene regulation at many sites throughout the mammalian genome and modulate the extent of gene silencing and hence severity in several triplet-repeat diseases.