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ctDNA monitoring using tumor-informed copy number analysis
Get PDFMethods to detect circulating tumor DNA (ctDNA) enable minimally invasive responsive monitoring of cancer dynamics. However, sensitive and cost-effective methods are still lacking. Current methods for detecting cancer signals in shallow whole-genome sequencing (sWGS) data from cell-free DNA (cfDNA) via copy number aberration (CNA) analysis typically have a limit of detection of approximately 3% tumor fraction (TF). We developed informCNA, a bioinformatics method that leverages CNA information from sWGS of tumor or pre-treatment plasma samples with high TF as references, enabling ctDNA detection down to 0.2% TF across multiple cancer types. In 177 serial plasma samples from 18 patients with ovarian cancer, informCNA showed high concordance with the standard serum protein marker CA-125 and identified recurrence a median of 3.7 months earlier than CA-125 test. These results demonstrate the potential of personalized CNA analysis through sWGS for estimating ctDNA burden, enabling precise and cost-effective disease monitoring and early detection of relapse
Lp–Lq boundedness of Fourier multipliers on quantum Euclidean spaces
No full textIn this paper, we study Fourier multipliers on quantum Euclidean spaces and obtain results on their Lp–Lq boundedness. On the way to get these results, we prove Paley, Hausdorff–Young–Paley, and Hardy–Littlewood inequalities on the quantum Euclidean space. As applications, we establish the Lp–Lq estimate for the heat semigroup and Sobolev embedding theorem on quantum Euclidean spaces. We also obtain quantum analogues of logarithmic Sobolev and Nash type inequalities
Methodological review of the design, objectives and sample size of Research for Patient Benefit (RfPB) applications that use an external randomised controlled pilot trial design: A protocol
Get PDF Background The National Institute for Health and Care Research accepts applications for pilot and feasibility studies to their Research for Patient Benefit (RfPB) programme. There has been limited work describing the design practices of these applications and funding status. Knowing some of the qualities which may contribute towards a pilot or feasibility study application successfully gaining funding could help researchers improve the quality of their applications. Therefore, this study describes the protocol for a review looking at the characteristics of funded and non-funded external pilot trial applications. In particular, the primary objective is to describe the planned sample size and sample size justifications. Methods The study will be conducted on 100 applications from Competition 31–37 with a randomised feasibility design, identified and given access to us by RfPB where the lead applicant has consented. We will screen these applications to identify the external pilot trials, first looking through the titles and then the full text. Following this, we will extract data on information such as medical area, study design, objective(s), sample size, sample size justification, and funding outcome stage one and two. Validation will be performed on 20% of the data extracted; discrepancies will be resolved by discussion or a third reviewer will decide if there is no consensus. We will use descriptive statistics to summarise quantitative data, and will analyse qualitative data using thematic analysis. Findings will be summarised through discussion with the project contributors to produce a reader-friendly guidance document. Discussion This work will provide a more complete picture of RfPB external randomised pilot and feasibility trials. The findings will assist researchers when planning their pilot trials, and could help improve the quality of submitted applications. Protocol Registration Open Science Framework protocol registration DOI: https://doi.org/10.17605/OSF.IO/PYKVG . </jats:sec
Effect of visual cues on the formation of spatial maps
No full textSpatial navigation is a fundamental cognitive process that enables animals to locate resources, avoid danger, and move efficiently through their environment. The hippocampal formation, with its specialized neural populations such as place cells, grid cells, and head direction cells, provides the neural substrate for constructing internal spatial representations, commonly referred to as cognitive maps. This thesis investigates how visual cues influence spatial coding, how spatial maps are formed in novel virtual environments, and how replay contributes to their stabilization. To address these questions, I combined a two-dimensional virtual reality (VR) navigation paradigm with in vivo electrophysiology recordings in mice, alongside quantitative analyses of neuronal activity and replay dynamics. Three main findings emerged. First, boundary related visual inputs were essential for stabilizing spatial firing, elevated walls supported stable place and grid cells representations, whereas patterned floor cues alone were insufficient. Second, during exposure to novel VR environments, place cells rapidly formed stable firing fields, followed by the gradual emergence of grid cell periodicity, revealing a temporal sequence in the de novo establishment of spatial maps. Third, hippocampal replay during sleep contributed to spatial map formation. Together, these results highlight the dominant role of boundary cues in anchoring spatial representations, the sequential development of place and grid cells codes in novel contexts, and the contribution of replay to spatial maps stabilization
Making an impression: Participant-led voice synthesis reveals the acoustic signatures of trait impressions.
Get PDFListeners rapidly form trait impressions from voices, inferring multiple person characteristics within milliseconds. We employed a novel method, Self-Steered Sound Synthesis (S4), to identify and compare the acoustic signatures underlying these impressions. Participants interactively used S4 to synthesise voices expressing six person characteristics - age, masculinity, health, attractiveness, dominance, and trustworthiness - by manipulating four perceptually salient acoustic dimensions: mean pitch, pitch excursion, breathiness, and formant spacing. Masculinity, older age, and dominance were conveyed by lowering mean pitch and formant spacing, consistent with projecting the impression of a large person, and by flattening the intonation. Physical health, attractiveness, and trustworthiness were conveyed by choosing less extreme and more "typical" acoustic properties. A second perceptual experiment confirmed that the synthesised voices from Experiment 1 indeed conveyed the intended person characteristics to an independent sample of listeners, and that listeners relied on similar acoustic cues for their evaluations. From a methodological perspective, we demonstrate the robustness of S4 and present convergent evidence from two drastically different approaches, thus providing a comprehensive account of impression formation that bridges voice production (or synthesis) and perception. From a theoretical perspective, our findings agree with the hypothesis that trait impressions occur within a continuous "trait space", highlighting the graded and intercorrelated nature of different person characteristics on a perceptual and conceptual level. We extend this framework by showing that not only perceptual judgements, but also the acoustic signatures of person characteristics show intercorrelations, thus integrating acoustic cues into perceptual models of voice perception
Health professional perspectives on vision screening in older adults who attend hospital following a fall: a focus group study
No full textSystematic evidence and policy review of how education and training best equips the care workforce for people with chronic neurological disorders
No full textSuperstring amplitudes from the field-theory limit: an n-point map at one loop
Get PDFAre perturbative superstring amplitudes for massless external states just an α′ dressing of super-Yang-Mills/supergravity? This is the case at tree level, where the worldsheet correlators at n points can be written in a natural worldsheet basis, such that the kinematic coefficients are BCJ numerators of super-Yang-Mills/supergravity amplitudes, with the non-trivial α′ dependence carried only by the Koba-Nielsen factor. Motivated by this construction, we present for the first time a complete worldsheet basis of one-loop superstring correlators at n points. All the kinematic coefficients associated to non-cusp basis elements are identified with pieces of one-loop BCJ numerators of super-Yang-Mills/supergravity. This determines the superstring correlators up to 15 points in terms of field theory. Starting at 16 points (modular weight 12), the worldsheet basis may include cusp forms, which vanish in the field-theory degeneration, such that the associated coefficients cannot be fixed in this manner. Therefore, the one-loop answer to our initial question is determined, at high multiplicity, by whether the coefficients of cusp basis elements vanish or not. As a by-product of our construction, we present new constraints on the field-theory limit that result from string modularity. These are expressed as additional relations among one-loop BCJ numerators in maximal super-Yang-Mills/supergravity starting at 6 points
