Yes / Background: The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and aspirin both have proof of concept for colorectal cancer chemoprevention, aligned with an excellent safety profile. Therefore, we aimed to test the efficacy of EPA and aspirin, alone and in combination and compared with a placebo, in individuals with sporadic colorectal neoplasia detected at colonoscopy. Methods: In a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial, patients aged 55–73 years who were identified during colonoscopy as being at high risk in the English Bowel Cancer Screening Programme (BCSP; ≥3 adenomas if at least one was ≥10 mm in diameter or ≥5 adenomas if these were <10 mm in diameter) were recruited from 53 BCSP endoscopy units in England, UK. Patients were randomly allocated (1:1:1:1) using a secure web-based server to receive 2 g EPA-free fatty acid (FFA) per day (either as the FFA or triglyceride), 300 mg aspirin per day, both treatments in combination, or placebo for 12 months using random permuted blocks of randomly varying size, and stratified by BCSP site. Research staff and participants were masked to group assignment. The primary endpoint was the adenoma detection rate (ADR; the proportion of participants with any adenoma) at 1 year surveillance colonoscopy analysed in all participants with observable follow-up data using a so-called at-the-margins approach, adjusted for BCSP site and repeat endoscopy at baseline. The safety population included all participants who received at least one dose of study drug. The trial is registered with the International Standard Randomised Controlled Trials Number registry, number ISRCTN05926847. Findings: Between Nov 11, 2011, and June 10, 2016, 709 participants were randomly assigned to four treatment groups (176 to placebo, 179 to EPA, 177 to aspirin, and 177 to EPA plus aspirin). Adenoma outcome data were available for 163 (93%) patients in the placebo group, 153 (85%) in the EPA group, 163 (92%) in the aspirin group, and 161 (91%) in the EPA plus aspirin group. The ADR was 61% (100 of 163) in the placebo group, 63% (97 of 153) in the EPA group, 61% (100 of 163) in the aspirin group, and 61% (98 of 161) in the EPA plus aspirin group, with no evidence of any effect for EPA (risk ratio [RR] 0·98, 95% CI 0·87 to 1·12; risk difference –0·9%, –8·8 to 6·9; p=0·81) or aspirin (RR 0·99 (0·87 to 1·12; risk difference –0·6%, –8·5 to 7·2; p=0·88). EPA and aspirin were well tolerated (78 [44%] of 176 had ≥1 adverse event in the placebo group compared with 82 [46%] in the EPA group, 68 [39%] in the aspirin group, and 76 [45%] in the EPA plus aspirin group), although the number of gastrointestinal adverse events was increased in the EPA alone group at 146 events (compared with 85 in the placebo group, 86 in the aspirin group, and 68 in the aspirin plus placebo group). Six upper-gastrointestinal bleeding events were reported across the treatment groups (two in the EPA group, three in the aspirin group, and one in the placebo group). Interpretation Neither EPA nor aspirin treatment were associated with a reduction in the proportion of patients with at least one colorectal adenoma. Further research is needed regarding the effect on colorectal adenoma number according to adenoma type and location. Optimal use of EPA and aspirin might need a precision medicine approach to adenoma recurrence. / Efficacy and Mechanism Evaluation Programme, a UK Medical Research Council and National Institute for Health Research partnership. / Research Development Fund Publication Prize Award winner, November 2018.

Yes / The aim of this study was to identify the potential impact of positive and negative dimensions of caregiving on caregiver well-being and satisfaction with life (SwL). This study used time-point one data from the Improving the experience of Dementia and Enhancing Active Life (also known as IDEAL)cohort study that involved 1,283 informal caregivers of people in the mild-to-moderate stages of dementia recruited from 29 sites within Great Britain. Multivariate linear regression modeling was used to investigate the associations between positive dimensions of caregiving (measured by caregiving competence and perceptions of positive aspects of caregiving), negative dimensions of caregiving (measured by caregiving stress and role captivity), and caregiver well-being and SwL. Lower well-being was associated with low caregiving competence (–13.77; 95% confidence interval [CI]:–16.67, –10.87), perceiving fewer positive aspects of caregiving (–7.67; 95% CI:–10.26, –5.07), high caregiving stress (–24.45; 95% CI:–26.94, –21.96), and high role captivity (–15.61; 95% CI:–18.33, –12.89). Lower SwL was associated with low caregiving competence (–4.61; 95% CI:–5.57, –3.66), perceiving fewer positive aspects of caregiving (–3.09; 95% CI:–3.94, –2.25), high caregiving stress (–7.88; 95% CI:–8.71, –7.06), and high role captivity (–6.41; 95% CI:–7.27, –5.54). When these four measures were combined within the same model, only positive aspects of caregiving and caregiving stress retained independent associations with well-being and SwL. Both positive and negative dimensions of caregiving were associated with caregiver well-being and SwL. Psychological therapies and interventions need to consider not only the negative aspects of caregiving but also positive caregiving experiences and their implications for caregiver well-being and SwL. / Research Development Fund Publication Prize Award winner, February 2019. The IDEAL data will be deposited with the UK Data Archive upon completion of the study. Details on how the data can be accessed will be made available on the project website www.idealproject.org.uk.

Yes / Motion in depth (MID) can be cued by high-resolution changes in binocular disparity over time (CD), and low-resolution interocular velocity differences (IOVD). Computational differences between these two mechanisms suggest that they may be implemented in visual pathways with different spatial and temporal resolutions. Here, we used fMRI to examine how achromatic and S-cone signals contribute to human MID perception. Both CD and IOVD stimuli evoked responses in a widespread network that included early visual areas, parts of the dorsal and ventral streams, and motion-selective area hMT+. Crucially, however, we measured an interaction between MID type and chromaticity. fMRI CD responses were largely driven by achromatic stimuli, but IOVD responses were better driven by isoluminant S-cone inputs. In our psychophysical experiments, when S-cone and achromatic stimuli were matched for perceived contrast, participants were equally sensitive to the MID in achromatic and S-cone IOVD stimuli. In comparison, they were relatively insensitive to S-cone CD. These findings provide evidence that MID mechanisms asymmetrically draw on information in precortical pathways. An early opponent motion signal optimally conveyed by the S-cone pathway may provide a substantial contribution to the IOVD mechanism. / Supported by the Biotechnology and Biological Sciences Research Council Grants BB/M002543/1 (to A.R.W.), BB/M001660/1 (to J.M.H.), and BB/M001210/1 (to M.B.). / Research Development Fund Publication Prize Award winner, May 2019.

Yes / The carbon (δ13C) and nitrogen (δ15N) isotope ratios of human bone collagen have been used extensively over the last 40 years to investigate the diet of past populations. It has become apparent that bone collagen can give an unreliable temporal dietary signature especially in juveniles. With higher temporal resolution sampling of collagen from tooth dentine, it is possible to identify short‐term changes in diet previously invisible in bone. This paper discusses the inherent problems of using bone collagen for dietary studies and suggests better sample choices which can make our interpretations more robust, using breastfeeding and weaning as an example. / The modern data was collected and analysed using funding from the Rank Prize Funds New Investigator Award and sponsorship from DB Orthodontics, Bradford. The Tooth Fairy team acknowledges the support of the National Institute for Health Research Clinical Research Network (NIHR CRN). / Research Development Fund Publication Prize Award winner, February 2020.

Yes / User-generated reviews of visitor attractions, on publicly available websites, such as Tripadvisor, are frequently used in tourism research but feature less often in published cultural heritage research. In this paper, we describe a qualitative analysis of the text from user-generated reviews of three peatland heritage landscapes in the United Kingdom – Ilkley Moor, Thorne and Hatfield Moors, and Shapwick Heath – to better understand the role tangible and intangible cultural heritage play in visitor perceptions and narratives of these sites. Our analysis indicates that visitors tend to emphasise natural over cultural heritage of peatland landscapes and hold plural, highly contextual and sometimes dissonant perceptions; there is no single story of peatlands. This presents both challenges and opportunities for building public appreciation of peatland cultural heritage. User-generated reviews offer, as-yet under-explored, potential data for use by heritage researchers and managers who seek to explore how visitors understand and use sites, and may also contribute to the emerging intangible heritage of heritage landscapes. / Research Development Fund Publication Prize Award winner, June 2021.

Yes / Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1–3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity. / Research Development Fund Publication Prize Award winner, May 2022.

Yes / Studies of nanosized forms of bismuth (Bi)-containing materials have recently expanded from optical, chemical, electronic, and engineering fields towards biomedicine, as a result of their safety, cost-effective fabrication processes, large surface area, high stability, and high versatility in terms of shape, size, and porosity. Bi, as a nontoxic and inexpensive diamagnetic heavy metal, has been used for the fabrication of various nanoparticles (NPs) with unique structural, physicochemical, and compositional features to combine various properties, such as a favourably high X-ray attenuation coefficient and near-infrared (NIR) absorbance, excellent light-to-heat conversion efficiency, and a long circulation half-life. These features have rendered bismuth-containing nanoparticles (BiNPs) with desirable performance for combined cancer therapy, photothermal and radiation therapy (RT), multimodal imaging, theranostics, drug delivery, biosensing, and tissue engineering. Bismuth oxyhalides (BiOx, where X is Cl, Br or I) and bismuth chalcogenides, including bismuth oxide, bismuth sulfide, bismuth selenide, and bismuth telluride, have been heavily investigated for therapeutic purposes. The pharmacokinetics of these BiNPs can be easily improved via the facile modification of their surfaces with biocompatible polymers and proteins, resulting in enhanced colloidal stability, extended blood circulation, and reduced toxicity. Desirable antibacterial effects, bone regeneration potential, and tumor growth suppression under NIR laser radiation are the main biomedical research areas involving BiNPs that have opened up a new paradigm for their future clinical translation. This review emphasizes the synthesis and state-of-the-art progress related to the biomedical applications of BiNPs with different structures, sizes, and compositions. Furthermore, a comprehensive discussion focusing on challenges and future opportunities is presented. / M.-A. Shahbazi acknowledges financial support from the Academy of Finland (grant no. 317316). P. Figueiredo acknowledges the Finnish Cultural Foundation for its financial support (decision no. 00190246). H. A. Santos acknowledges financial support from the HiLIFE Research Funds, the Sigrid Juse´lius Foundation, and the Academy of Finland (grant no. 317042). / Research Development Fund Publication Prize Award winner, Jan 2020.

Yes / This paper presents the development of a new chatter model using measured cutting forces instead of a mathematical model with empirical nature that describes them. The utilisation of measured cutting forces enables the prediction of real-time chatter conditions and stable machining. The chatter model is validated using fast Fourier transform (FFT) analyses for detection of chatter. The key contribution of the developed chatter model is that it can be incorporated in digital twins for process monitoring and control in order to achieve greater material removal rates and improved surface quality in future industrial applications involving machining processes. / Research Development Fund Publication Prize Award winner, Sep 2020.

Yes / Herein, we report a catalyst-free ‘click’ reaction: metal-free [2 + 2] cycloaddition–retro-electrocyclisation (CA–RE) of arylynamines with the sluggish acceptor tetracyanoquinodimethane (TCNQ) to provide orthogonal electron-push–pull light-harvesting small molecules: N-heterocyclic dicyanoquinodimethane-substituted methylene malononitriles. Ynamines are reactive alkynes and tend to induce over-reactions with the CA–RE adducts. The reactivity of arylynamines was balanced properly by ensuring the electrondensity of the nitrogen atom was delocalised more over the aromatic rings than the triple bond. / This work was supported by Guangxi Natural Science Foundation (2020JJA120032). / Research Development Fund Publication Prize Award winner, April 2022.

Yes / In this conceptual paper, we respond to the calls for broader theoretical approaches that can coherently demonstrate a high degree of conceptual sensitivity to multiple combinations of institutional factors influencing women's informal entrepreneurship (WIE) and related agency. We do so by integrating constructs of gender and gender inequality with those of institutional logics and institutional voids. We find that a refined understanding of institutional voids is required to pave the way for a meaningful theoretical integration and empirical application of the related conceptualizations. We offer such a revised definition by placing formal and informal logics (rather than institutions) at the heart of it. In our theorizing, we propose that gender interplaying with formal and informal institutional logics create varying degrees of obscure and unique institutional voids that shape WIE prevalence. The proposed harmonized theoretical lens provides researchers with flexible yet consistent guidance for conducting context-specific empirical work that can coherently advance understanding of underlying logics shaping WIE and related agency. / Research Development Fund Publication Prize Award winner, Jan 2023.