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Constructing witnesses for lower bounds on behavioural distances
Get PDFBehavioural distances provide a robust alternative to notions of equivalence such as bisimilarity in the context of probabilistic transition systems. They can be defined as least fixed points, whose universal property allows us to exhibit upper bounds on the distance between states, showing them to be at most some distance apart. In this paper, we instead consider the problem of bounding distances from below, showing states to be at least some distance apart. Contrary to upper bounds, it is possible to reason about lower bounds inductively. We exploit this by giving an inductive derivation system for lower bounds on an existing definition of behavioural distance for labelled Markov chains. This is inspired by recent work on apartness as an inductive counterpart to bisimilarity. Proofs in our system will be shown to closely match the behavioural distance by soundness and (approximate) completeness results. We further provide a constructive correspondence between our derivation system and formulas in a modal logic with quantitative semantics. This logic was used in recent work of Rady and van Breugel to construct evidence for lower bounds on behavioural distances. Our constructions provide smaller witnessing formulas in many examples
Feasibility and implementation of INTERVAL-GAP4: a global randomised controlled trial of intense hybrid-supervised/self-managed versus self-directed exercise for metastatic prostate cancer
Get PDFBACKGROUND AND OBJECTIVE: Physical activity is associated with a lower risk of mortality in men with prostate cancer (PC); yet, randomised controlled trials with survival endpoints are nonexistent. INTense ExeRcise for surviVAL-Global Action Plan 4 (INTERVAL-GAP4) was a global phase 3 trial designed to test whether structured, hybrid-supervised/self-managed exercise improves survival in men with metastatic PC. The trial was stopped early due to poor accrual. This paper reports feasibility and implementation outcomes.
METHODS: Men with metastatic PC were randomised (1:1) to a supervised/self-managed moderate- to high-intensity resistance and aerobic programme (three sessions per week for 2 yr) or to self-directed exercise. We evaluated site activation, recruitment, year 1 adherence, adverse events, and barriers to global trial feasibility. Efficacy outcomes-including survival, physical fitness, and biomarker results-will be reported separately.
KEY FINDINGS AND LIMITATIONS: Of 21 activated sites across seven countries, 13 (62%) randomised patients. Of 938 patients approached, 232 (25%) consented and 145 (15%) were randomised (75 in the intervention and 70 in the control group) between April 2016 and February 2023. The median age was 70 yr (range: 44-89 yr). The study closed early after reaching 17% of the intended target. The median adherence in the intervention arm was 84% (interquartile range: 61-95%), with no difference between metastatic castrate-resistant and hormone-sensitive PC. At 12 mo, 58% of intervention participants met exercise guidelines versus 24% of controls. In year 1, 162 adverse events occurred in the intervention group and 109 in the control group; 19 adverse events were study related, all in the intervention arm. The major feasibility challenges included administrative burden, infrastructure limitations, logistics of supervised exercise delivery, and coronavirus disease 2019 disruptions.
CONCLUSIONS AND CLINICAL IMPLICATIONS: While high adherence to a demanding exercise programme was achieved in selected metastatic PC patients, global recruitment proved difficult. Future large-scale exercise-oncology trials require streamlined protocols, realistic timelines, and greater alignment with site resources. Implementation science research is needed to support integration of exercise into routine advanced cancer care. A forthcoming paper will present the trial's survival and physical fitness efficacy outcomes.
PATIENT SUMMARY: In this report, we describe the feasibility of a centrally coordinated, global clinical trial of hybrid-supervised/self-managed versus self-directed exercise for men with metastatic prostate cancer. We report trial implementation as mixed across the world, while exercise session adherence was high among men receiving the intervention. However, of the patients approached, 53% declined to participate in the study, and those enrolled were likely more motivated and willing to exercise. Those who participated varied in age, had other health conditions, were receiving multiple medications, and were at different treatment stages after a diagnosis of metastatic prostate cancer. Recent guidelines provide a framework for integrating exercise programming into clinical care for patients with advanced cancer. Further implementation science research is needed to help patients with advanced cancer exercise safely and effectively as part of their cancer care
Seeing into Hi-C: How our scientific connectivity revealed the close connections in our DNA to be a work of art
Get PDFScientific data can be beautiful. An example where the data itself have a particularly striking appearance even before any scientific meaning has been ascribed is the so-called “Hi-C” chromatin interaction map with its distinct checker-board patterns which when combined with simulations have revealed the complex structure of the folded genome. Here, we describe an art-science collaboration which arose through combining local and global inter-personal connections, and which illustrates the equivalent short- and long-range contacts within folded genomes
Breeding for Multipurpose Sugarcane:Evaluating Agronomic and Cell-Wall Traits for Sugar, Biomass, and Second-Generation Ethanol Production
Get PDFIntermedial afterlives of the Arma Christi in Orlando Gibbons’s ‘See, see the word is incarnate’
Get PDFWe propose that Orlando Gibbons’s consort anthem ‘See, See the Word is Incarnate’ is linked to a wider phenomenon in visual culture surrounding the imagery of the instruments of Christ’s Passion, the arma Christi. Taking a bold interdisciplinary approach, we use close reading to show how this visual tradition manifested in intermedial ways. This case study is indicative of a type of exchange between art forms that was fundamental to English artistic practice and devotional experience. Our analysis connects this music to the Passion’s long history with sight, exploring broader contexts for Gibbons’s invocation to ‘see’. We view this song as an experiment in musical intermediality, exemplifying the fluidity between the visual, textual, and musical practices of early modern England. It expands current understanding of the piece’s connections to contemporary visual culture, while examining music’s potential as a potent act of extraordinary meditation within England’s complex post-Reformation confessional landscape
Closing the Cartesian bureau de change
Get PDFIn A Philosophy for the Science of Animal Consciousness, Walter Veit sets out a Darwinian framework for understanding consciousness. He distinguishes various dimensions of consciousness, explores their distribution in different species, and traces their roots to an ancient system of hedonic valence, which evolved to solve complex problems of action selection in early animals. This approach places Veit firmly within a new ‘post-Cartesian’ paradigm for consciousness science, which treats consciousness as a complex functional state, which can be studied by standard scientific means – in contrast to the traditional Cartesian paradigm, which focused on irreducibly subjective qualia and the ‘hard problem’ they present. However, there are places where Veit’s discussion displays residual Cartesian influence. Veit continues to use Cartesian terms such as ‘qualia’, and he suggests that states of hedonic valence play their functional role in virtue of their ‘feel’, implying a subjective realm – a ‘Cartesian bureau de change’ – where intrinsic value is felt and reacted to. This weakens Veit’s presentation, and I urge him to commit to a thoroughly functionalist account. The Cartesian and post-Cartesian paradigms are incommensurable, and in order to achieve a Darwinian revolution in consciousness studies, the concept of an irreducibly subjective mental realm must be completely abandoned
Light sheet imaging in granular materials: interdisciplinary opportunities
Get PDFGranular materials, ubiquitous in geophysics, chemical engineering, biophysics and soft matter physics, present unique challenges for optical imaging due to their opaque and heterogeneous nature. This perspective paper provides a comprehensive overview of opportunities in Light Sheet Microscopy (LSM) techniques for imaging granular materials, emphasizing refractive index matching as a critical tool for visualizing internal deformations and flow dynamics. By matching the refractive indices of solid particles and surrounding fluids, researchers can create “transparent soils” or analogous systems, enabling detailed examination of particle interactions, strain fields, and fluid flow. To comprehensively introduce opportunities for future research, the review explores the evolution of LSM, from early broadband light sources to modern laser and LED-based systems, highlighting advancements in wavefront shaping and contrast generation through scattering and fluorescence. The paper also surveys some innovative approaches for LSM and index matching, such as Sephadex spheres and cryolite. Emerging techniques, such as wavefront shaping and three dimensional imaging with event cameras, are presented as promising avenues for future research. Additionally, the review connects granular imaging to biological systems, demonstrating its relevance for studying microbial motility, biofilm growth, and tissue engineering. This perspective paper aims to guide and inspire researchers in selecting and refining LSM techniques for advancing the understanding of complex particulate systems
Do weak intellectual property rights regimes affect foreign multinational firms' technology exploration? The moderating role of function-related and location-related experience
Get PDFExisting literature suggests that weak intellectual property rights (IPR) regimes are not conducive to innovation intensive activities. However, evidence of technology exploration activities by multinational companies (MNCs) in emerging countries challenges this view. We address this puzzle by examining how host-country IPR regimes influence MNCs' technology exploration, distinguishing between technology-seeking (TS) and home-base augmenting (HBA) activities. Drawing on organizational experience and learning theories, we also test the moderating role of MNCs' function-related (innovation function-specific and function-generic) and location-related (host country-specific and country-generic) international experience. Using PATSTAT patent data for 91 U.S. computer and electronics firms in the period 2001–2018, we find that weaker IPR protection is associated with a higher proportion of HBA initiatives. This challenges the conventional view that strong IPR regimes are indispensable for technology exploration. Moreover, we show that MNCs with extensive function-specific experience in the host and other foreign countries better navigate diverse IPR environments, making their technology exploration activities less affected by the strength of the host-country IPR regime
Static assessment of hybrid double‐lap bolted joints with additively manufactured 316L plates
Get PDFThe present study examines the static response and evaluates the accuracy of design standards and selected literature-based design criteria in estimating the load capacity of the inner plates of double-lap shear bolted connections in single- and double-bolt configurations. The analysis is based on 70 experiments previously reported by the authors, including conventional and additively manufactured inner plates produced by wire arc additive manufacturing and selective laser melting. While additively manufactured plates exhibited load capacities comparable to conventional plates, they generally showed reduced ductility. Experimental load capacities are compared against the European standards EC3-1-8 and EC3-1-4 and the American standard AISC 370. Although originally developed for carbon steel, EC3-1-8 provided the most accurate estimations, whereas EC3-1-4 and AISC 370 consistently overestimated the load capacity. Literature-based equations showed the closest agreement, highlighting limitations in current standards for additively manufactured bolted plates
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