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Adapting the design of the ongoing RAMPART trial in response to external evidence : an example for trials which take many years to run and report
Get PDFFunding: Kidney Cancer UK; Cancer Research UK. The authors would like to thank RAMPART participants and their families for taking part in the trial, all the investigators and site teams at the 74 RAMPART sites in UK, Australia, France and Spain for their efforts and their industry partner Astra Zeneca for their support. Babak Choodari-Oskooei was supported by the Medical Research Council (MRC) grant numbers MC_UU_00004_09 and MC_UU_123023_29. IDD is supported in part by an Australian NHMRC Investigator Grant (2016274).Clinical trials to establish the efficacy of new agents in the adjuvant cancer setting typically take many years to complete. During that time, external factors can impact recruitment and reporting plans. An example is a new standard of care becoming available during the recruitment period. In this paper we describe how we modified the design of the RAMPART trial (NCT03288532) which was set up to investigate immune checkpoint inhibitor therapy in the adjuvant renal cancer setting. The trial had been initiated when no globally accepted adjuvant strategy after nephrectomy existed. A subsequent change in the standard of care for many patients with early renal cancer meant it was no longer feasible to continue to recruit. We needed to find a way to maximise the contribution that RAMPART participants could make to the evidence base for immune checkpoint inhibitor therapy without introducing bias or detriment to the integrity of the trial results. We describe how we agreed and incorporated all design and timeline changes while remaining blinded to accumulating data within the trial, thus protecting the reliability of the future results. We share details of our design modifications to guide others who may have similar experiences, particularly as more agents and combinations of agents are developed and investigated in similar adjuvant settings.Peer reviewe
Participation in a nationwide workplace step count competition is associated with improved physical fitness and mental wellbeing : a longitudinal, repeated-measures analysis
Get PDFFunding: This research was completed as part of SW’s PhD project, which was funded by the Scottish Graduate School of Social Science (ESRC) and Paths for All (Registered Scottish Charity No SC025535).Background: The widely recognized health benefits of physical activity have led to the development of programs designed to increase activity levels within workplaces, where inactivity is often prevalent. We aimed to evaluate how participation in a Scotland-wide workplace walking program (Step Count Challenge [SCC]) influenced participants’ physical fitness and mental well-being. Methods: A 3-part multistudy design was employed, each using the 2-minute step test and Short Warwick-Edinburgh Mental Well-Being Scale to measure physical fitness and mental well-being, respectively. Study 1 (Spring, 8 wk, N = 475) and study 2 (Autumn, 4 wk, N = 336) were repeated-measures online-based nationwide cohort studies in 2021, and study 3 (N = 38) was an in-person experimental design with a control group in 2023. Results: Studies 1 and 2 found significant improvement in physical fitness (Spring: P < .001, η2 = .19; Autumn: P = .014, η2 = .13) and mental well-being (Spring: P < .001, η2 = .13; Autumn: P = .007, η2 = .05). Study 3 found a significant group × time interaction for physical fitness (P = .018, η2 = .172) such that the SCC group significantly improved over time (P = .042, η2 = .131) and found no significant differences for mental well- being. Conclusions: The findings of studies 1 and 2 demonstrate that participation in SCC is associated with a positive effect on physical fitness and mental well-being regardless of seasonal and duration differences. Study 3 also showed improvement in physical fitness, with a significantly greater increase for those who participated in SCC. This supports the promotion of future workplace walking programs.Peer reviewe
Plasmodesmata act as unconventional membrane contact sites regulating intercellular molecular exchange in plants
Get PDFFunding: This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (projects 772103-BRIDGING to E.M.B. and 101001097-LIPIDEV to Y.J.), the National Agency for Research (grants ANR-18-CE13-0016 STAYING-TIGHT to E.M.B. and Y.J., ANR-2020-CE20-0002 3C TomFruit Growth to E.M.B., ANR-21-CE13-0016-01 DIVCON to A.T. and E.M.B., and ANR-18-CE13-0025-02 caLIPSO to Y.J.), the Human Frontier Science Program (project RGP0002/2020 to E.M.B.), the French Government in the framework of the IdEX Bordeaux University “Investments for the Future” program/GPR Bordeaux Plant Sciences (E.M.B.), the Swiss National Science Foundation (project 31003A_179159 to M.B.), Research Foundation-Flanders grant G002121N to E.R., the HORIZON-MSCA-2023-PF-01 project 101152141-BRACTION to Y.L., and Projet Emergents FlowValve University of Bordeaux to M.S.Membrane contact sites (MCSs) are fundamental for intracellular communication, but their role in intercellular communication remains unexplored. We show that in plants, plasmodesmata communication bridges function as atypical endoplasmic reticulum (ER)-plasma membrane (PM) tubular MCSs, operating at cell-cell interfaces. Similar to other MCSs, ER-PM apposition is controlled by a protein-lipid tethering complex, but uniquely, this serves intercellular communication. Combining high-resolution microscopy, molecular dynamics, and pharmacological and genetic approaches, we show that cell-cell trafficking is modulated through the combined action of multiple C2 domains transmembrane domain proteins (MCTPs) 3, 4, and 6 ER-PM tethers and phosphatidylinositol-4-phosphate (PI4P) lipid. Graded PI4P amounts regulate MCTP docking to the PM, their plasmodesmata localization, and cell-cell permeability. SAC7, an ER-localized PI4P-phosphatase, regulates MCTP4 accumulation at plasmodesmata and modulates cell-cell trafficking capacity in a cell-type-specific manner. Our findings expand MCS functions in information transmission from intracellular to intercellular cellular activities.Peer reviewe
Donations to St Andrews, 1700-1900 : methods and definitions
Get PDFFunding: St Andrews and the Legacies of Empire fellowship.This working paper explains the ‘Methods’ and ‘Definitions’ underpinning ‘Section 3: Where did the University’s Money come from?’ of the final report on St Andrews and the Legacies of Empire (2024). The sections below formed the opening sections of a report on ‘Donations to St Andrews, 1700-1900’ presented to the Legacies of Empire steering group in September 2023 (which was itself an update on an internal report from December 2022)
Representations of extensions of simple groups
Get PDFFunding: The first author is an EPSRC Postdoctoral Fellow (EP/X011879/1).Feit and Tits (1978) proved that a nontrivial projective representation of minimal dimension of a finite extension of a finite nonabelian simple group G factors through a projective representation of G, except for some groups of Lie type in characteristic 2; the exact exceptions for G were determined by Kleidman and Liebeck (1989). We generalise this result in two ways. First we consider all low-dimensional projective representations, not just those of minimal dimension. Second we consider all characteristically simple groups, not just simple groups.Peer reviewe
The Fireblight menace : knowledge communities and their response to crop disease in the Anglo-world, 1880-1939
Get PDFThis thesis utilises the orchard disease ‘Fireblight’ as a means to explore the various communities involved in the creation and communication of horticultural knowledge in the Anglo-world (particularly the USA, Canada, and New Zealand) between 18801939. In the nineteenth century, Fireblight ravaged orchards in the United States and Canada, swiftly becoming endemic. In 1919, it spread to New Zealand, the first time it was recorded outside North America. Studying Fireblight enables us to shift the focus of histories of imperial horticulture and agricultural science from Britain’s tropical colonies to the dominions, and into a wider ‘Anglo-world' in which the British state was far less involved in directing scientific research. By investigating how the various communities of scientists, fruitgrowers, politicians, and civil servants, in Canada, the United States, and New Zealand, developed their understandings of how to deal with this culturally and biologically distinctive crop disease, this thesis explores both how each community developed a consensus, and also how knowledge moved between these communities. Each of these heterogenous groups had to navigate the interplay of practical and theoretical scientific knowledge concerning Fireblight in their efforts to claim expertise. The fruitgrowing communities and scientific institutions of the United States and Canada grew up with Fireblight, and expertise and experience was shared between both communities. In contrast, when the disease reached New Zealand, the relative infancy of the fruitgrowing sector meant civil servants and government scientists could claim greater expertise than fruitgrowers. Thus, the contrast between North America and New Zealand illustrates not only that scientists, fruitgrowers, and civil servants were all involved in shaping knowledge creation and communication practices, albeit with different priorities, but that the relationships between those communities depended on place and time
Probing moiré electronic structures through quasiparticle interference
Get PDFFunding: LCR and PW acknowledge funding from the Leverhulme Trust through Research Project Grant RPG-2022-315. This work used computational resources of the Cirrus UK National Tier-2 HPC Service at EPCC (http://www.cirrus.ac.uk) funded by the University of Edinburgh and EPSRC (EP/P020267/1).Moiré lattices are a general feature of bilayer structures, where an additional periodic superstructure is generated by either lattice mismatch or from a twist angle. They have been shown to stabilise new ground states, including unconventional superconductivity and Mott insulating phases, attributed to strong electron correlations. However, controlling these interactions requires a detailed understanding of the low energy electronic structure which is lacking so far. Probing the electronic structure is challenging due to sample inhomogeneity, the low characteristic energy scales involved and small sample sizes. Through quasiparticle interference (QPI) imaging, scanning tunneling microscopy (STM) can overcome many of these challenges but requires detailed modelling to extract the k-space electronic structure. Here, we present realistic calculations of QPI in twisted bilayer structures, which accounts for the effect of the long range moiré lattice on the electronic structure as well as it’s interaction at a defect. These calculations reveal that while the moiré supercell significantly reduces the size of the Brillouin zone, the QPI scattering vectors retain characteristics of the individual monolayers with distinct perturbations from the twisted geometry that can be directly linked back to the electronic structure. The procedure introduced here provides a general framework to use QPI to determine the low energy electronic structure in moiré lattice systems.Peer reviewe
Youth unleashed : museums as platforms for heritage and climate dialogue
No full textFunding: ‘Shared Island Stories Between Scotland and the Caribbean: Past, Present, Future’ is a five-year research project selected by the European Research Council (ERC) and funded by UK Research and Innovation (UKRI) with reference EP/ X023036/1. It is coordinated by the School of Art History at the University of St Andrews.As the climate emergency intensifies, youth-led movements worldwide are pressuring governments and societies to take urgent climate action. However, young people from communities disproportionately impacted by the climate emergency, such as the Caribbean, the Asia-Pacific Islands, and Indigenous communities, remain underrepresented. This article presents two museum-based projects: the University of St Andrews-led Shared Island Stories research project and the International Committee of Museology (ICOFOM)'s global youth workshops. The first uses transnational exchanges between Scotland and Barbados to empower young people as Youth Ambassadors, fostering cultural heritage preservation and climate justice. The second engages youth from 18 countries and territories in museum-based dialogues on climate action aligned with the UN Sustainable Development Goals (SDGs). Current museum policies frequently overlook barriers faced by young people, limiting meaningful engagement and missing critical opportunities to harness their energy and creativity (Kids in Museums 2024; Yates et al. 2022; Madgin et al. 2016). Both initiatives employ participatory action research and critical pedagogy, enhancing young people's skills and positioning them as active participants in climate solutions. These projects illustrate that inclusive museum practices aimed at amplifying youth voices are essential for achieving climate justice and fostering sustainable, equitable futures.Peer reviewe
Spatial myopia, financial hubs and the 'golden triangle' : tracing the uneven landscape of international equity investments in the UK
Get PDFFunding: This manuscript reports findings from an Economic and Social Research Council (ESRC) project: ‘Understanding how constraints on access to finance and under-investment impact on productivity growth in smaller firms’ (ES/W010259/1). While the authors wish to acknowledge the funding received for the project from the ESRC, the views in the paper are strictly those of the authors alone.The entrepreneurial finance literature has hitherto largely neglected the role of non-Indigenous equity finance across different territorial jurisdictions. Invoking the concept of spatial myopia, this paper examines the role played by this specialist form of finance within different locations and how a firm's relative geographic location within a national economy plays a fundamental determinant shaping their ability to obtain this form of specialist equity funding. In particular, this study explores the spatial dynamics of international equity investments, with a specific focus on the UK's six major financial EE hubs. By integrating firm-level data from Crunchbase with city-level economic indicators, the analysis employs a multilevel mixed-effects probit regression model to assess the probability of firms attracting international investors. Our findings reveal that the famous ‘Golden Triangle’ of London, Cambridge and Oxford remain dominant in terms of attracting international equity investments. Spatial myopia significantly influences investment patterns, with increased distance from the Golden Triangle correlating with reduced probabilities of securing international equity finance. However, no distinct advantages are observable for early and late-stage ventures within the triumvirate compared to the other financial hubs. We conclude that overcoming myopic decision-making in international equity investors is a non-trivial policy objective to address.Peer reviewe
exoALMA. XII. Weighing and sizing exoALMA disks with rotation curve modelling
Get PDFFunding: J.B. acknowledges support from NASA XRP grant No. 80NSSC23K1312. M.B., D.F., and J.S. have received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (PROTOPLANETS, grant agreement No. 101002188). Computations by JS have been performed on the “Mesocentre SIGAMM” machine, hosted by Observatoire de la Cote d’Azur. P.C. acknowledges support by the Italian Ministero dell’Istruzione, Università e Ricerca through the grant Progetti Premiali 2012—iALMA (CUP C52I13000140001) and by the ANID BASAL project FB210003. S.F. is funded by the European Union (ERC, UNVEIL, 101076613) and acknowledges financial contribution from PRIN-MUR 2022YP5ACE. M.F. is supported by a Grant-in-Aid from the Japan Society for the Promotion of Science (KAKENHI: No. JP22H01274). J.D.I. acknowledges support from an STFC Ernest Rutherford Fellowship (ST/W004119/1) and a University Academic Fellowship from the University of Leeds. Support for AFI was provided by NASA through the NASA Hubble Fellowship grant No. HST-HF2-51532.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555. C.L. has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 823823 (DUSTBUSTERS) and by the UK Science and Technology Research Council (STFC) via the consolidated grant ST/W000997/1. C.P. acknowledges Australian Research Council funding via FT170100040, DP18010423, DP220103767, and DP240103290. G.L. has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No. 823823 (DUSTBUSTERS) and from PRIN-MUR 20228JPA3A. G.R. acknowledges funding from the Fondazione Cariplo, grant No. 2022-1217, and the European Research Council (ERC) under the European Union’s Horizon Europe Research & Innovation Programme under grant agreement No. 101039651 (DiscEvol). H-.W.Y. acknowledges support from the National Science and Technology Council (NSTC) in Taiwan through grant NSTC 113-2112-M-001-035- and from the Academia Sinica Career Development Award (AS-CDA-111-M03). G.W.F. acknowledges support from the European Research Council (ERC) under the European Union Horizon 2020 research and innovation program (grant agreement No. 815559 (MHDiscs)). G.W.F. was granted access to the HPC resources of IDRIS under the allocation A0120402231 made by GENCI. Support for BZ was provided by The Brinson Foundation.The exoALMA large program offers a unique opportunity to investigate the fundamental properties of protoplanetary disks, such as their masses and sizes, providing important insights into the mechanism responsible for the transport of angular momentum. In this work, we model the rotation curves of CO isotopologues 12CO and 13CO of 10 sources within the exoALMA sample, and we constrain the stellar mass, the disk mass, and the density scale radius through precise characterization of the pressure gradient and disk self-gravity. We obtain dynamical disk masses for our sample by measuring the self-gravitating contribution to the gravitational potential. We are able to parametrically describe their surface density, and all of them appear gravitationally stable. By combining dynamical disk masses with dust continuum emission data, we determine an averaged gas-to-dust ratio of approximately 400, not statistically consistent with the standard value of 100, assuming optically thin dust emission. In addition, the measurement of the dynamical scale radius allows for direct comparison with flux-based radii of gas and dust. This comparison suggests that substructures may influence the size of the dust disk and that CO depletion might reconcile our measurements with thermochemical models. Finally, with the stellar mass, disk mass, scale radius, and accretion rate, and assuming self-similar evolution of the surface density, we constrain the effective αS for these systems. We find a broad range of αS values ranging between 10−5 and 10−2.Peer reviewe
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