Trinity College London

Abstract Background: Detection of circulating tumour DNA (ctDNA) in plasma predicts future recurrence in early breast cancer (EBC). Previous studies have relied on tumour-informed approaches with personalised assays. In this study, we performed orthogonal testing on plasma samples collected prospectively in the c-TRAK-TN study to compare a tissue-free assay with digital droplet PCR (ddPCR) for ctDNA analysis. Methods: c-TRAK-TN recruited 161 patients with early triple negative breast cancer (TNBC) deemed clinically high risk of relapse. Patients underwent ctDNA analysis by ddPCR starting within 4 weeks of completion of treatment and continuing every 3 months for up to 2 years. ddPCR tracked 1 or 2 patient specific variants as previously described. We further analysed 1062 timepoints from a total of 159 patients (median 7 per patient, range 1-11) using Guardant Reveal assay, a tissue-free approach that exploits differential methylation patterns in breast cancer compared with normal tissue. Results: Samples were successfully analysed from 95.3% (1012/1062) timepoints from 159 patients with the tissue-free Reveal assay. CtDNA was detected in 34.0% (54/159) of patients in at least 1 timepoint, with a median methylation tumour fraction of 0.266% (range 0.002 to 51.0%). Detection of ctDNA with the tumour agnostic assay strongly associated with future risk of relapse (HR 20.62, p<0.0001; logrank). Of patients who relapsed by 24 months follow up, 89.5% (34/38) of relapses were detected by prior ctDNA analysis. There were 159 patients available for comparison between ddPCR and the tissue-free assay (Reveal), in 1005 timepoints (median 7 per patient, range 1-11). Concordant test results were observed in 950/1005 timepoints with an overall agreement rate of 94.5%. In this cohort, 63.5% (101/159) of patients did not have ctDNA detected by either assay; 26.4% (42/159) had ctDNA detected by both assays and 10.1% (16/159) had discordant results. Of those detected, 44.8% (26/58) were detected by the tissue-free assay first and 6.9% (4/58) by ddPCR (p<0.0001, Fisher exact test). The median time from first detection of ctDNA to relapse for the tissue-free assay was 7.9 months (95% confidence interval (CI): 5.7-10.5 months) compared to ddPCR assay with 5.7 months (95% CI: 2.9-9.7 months) (HR = 0.6, p=0.0574; mixed effects cox model). Conclusion: Detection of ctDNA with a tissue-free assay anticipated relapse with high accuracy, in patients with early TNBC. The tissue-free assay frequently detected ctDNA at an earlier timepoint than ddPCR, trending towards a longer lead time from detection of ctDNA to relapse. Tissue-free approaches might offer simpler workflows for ctDNA analysis than tumour-informed approaches, and further assessment in clinical trials is warranted. Citation Format: N. Cunningham, R. J. Cutts, C. Swift, K. Dunne, M. Dewan, L. Kilburn, K. Goddard, P. Hall, C. Harper-Wynne, T. Hickish, I. Macpherson, A. Okines, A. Wardley, S. Waters, C. Palmieri, M. Winter, J. Bliss, D. Dustin, M. Ellis, I. Garcia- Murillas, N. C. Turner. Tissue-free circulating tumour DNA detection in patients with early triple negative breast cancer from the c-TRAK-TN trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr RF3-05.

Abstract Hallucinations are significant symptoms in psychiatric and neurodegenerative diseases, that may indicate advanced disease progression or worse disease forms. They are also frequent in healthy individuals, especially elderly or bereaved. Despite their relevance, studying hallucinations in controlled laboratory conditions remains challenging given the limited procedures inducing clinically relevant hallucinations. We have previously developed a robotics-based protocol capable of inducing a specific clinically relevant hallucination, presence hallucination (PH), in both healthy individuals and patients. Using this approach, we have systematically investigated the sensitivity and intensity of PH-induction, as well as its effects on various sensory, behavioral and cognitive aspects. In the present study, we pooled individual-participant data from 26 in-house experiments (totaling 580 individuals) and conducted a Bayesian analysis to estimate effects and moderators of PH-induction. PH-induction was reliably induced with a medium effect-size, and individuals with schizotypal traits were more sensitive. Furthermore, we identified that PH-induction may not strongly depend on altered agency, but found a synergistic relationship between passivity and induced PH. Collectively these results elucidate the role of somatomotor processes in aberrant own body perceptions, advance understanding of psychosis, and provide powerful statistical priors for future studies.

The 2025 ISSAC conference in Guanajuato, Mexico, marks the 50th event in this significant series, making it an ideal moment to reflect on the field’s history. This paper reviews the formative years of symbolic computation up to 1975, fifty years ago. By revisiting a period unfamiliar to most current participants, this survey aims to shed light on once-pressing issues that are now largely resolved and to highlight how some of today’s challenges were recognized earlier than expected.

Antibiotic resistance poses a global health crisis. In order to develop new antibiotic agents, it is crucial to identify drug targets in multidrug-resistant bacteria. Criteria for such a target are an α-helical, essential membrane protein, that is non-homologues with the human membrane proteome, and present across multiple bacterial species. Using a stepwise subtractive genomics approach, the membrane protein F0F1 ATP synthase subunit C was identified as a non-human analogues drug target that is present in 11 bacterial species.

Acute decompensated aortic stenosis is an increasingly common condition associated with a high rate of morbidity, mortality, and health care resource utilization. Among patients with acute decompensated aortic stenosis, this study aimed to assess the impact of time to transcatheter aortic valve implantation (TAVI) on outcomes, hypothesizing that longer durations are associated with worse outcomes. Using a single-center registry, patients with their first presentation of acute decompensated aortic stenosis who underwent an urgent TAVI during their index admission were included. Time to TAVI was defined as the number of days between hospital admission and TAVI. The primary composite outcome was heart failure hospitalization or all-cause mortality. The secondary composite outcome was heart failure hospitalization or cardiovascular mortality. A total of 276 patients were included in this study: age 84 (79-88) years, male sex 63.7%, patients requiring cardiopulmonary organ support 3.6%, aortic valve area 0.7 (0.5-0.8) cm2, and left ventricular ejection fraction 55 (37-57)%. Baseline characteristics were similar between patients stratified according to the median time to TAVI (22 [13-32] days). Over a follow-up of 4.6 (3.6-5.7) years, the primary and secondary outcomes occurred in 58% and 35% of patients, respectively. After adjusting for comorbidities, mean gradient, and cardiopulmonary organ support, time to TAVI was associated with both the primary (hazard ratio for every 5 days, 1.09 [95% CI, 1.04-1.16]; P=0.001) and secondary outcomes (hazard ratio for every 5 days, 1.08 [95% CI, 1.01-1.16]; P=0.023). In patients with acute decompensated aortic stenosis, longer time to TAVI was associated with an increased risk of adverse events at mid-term follow-up.

Integrated tasks are often used in higher education (HE) for diagnostic purposes, with increasing popularity in lingua franca contexts, such as German HE, where English-medium courses are gaining ground. In this context, we report the validation of a new rating scale for assessing reading-into-writing tasks. To examine scoring validity, we employed Weir’s (2005) socio-cognitive framework in an explanatory mixed-methods design. We collected 679 integrated performances in four summary and opinion tasks, which were rated by six trained student raters. They are to become writing tutors for first-year students. We utilized a many-facet Rasch model to investigate rater severity, reliability, consistency, and scale functioning. Using thematic analysis, we analyzed think-aloud protocols, retrospective and focus group interviews with the raters. Findings showed that the rating scale overall functions as intended and is perceived by the raters as valid operationalization of the integrated construct. FACETS analyses revealed reasonable reliabilities, yet exposed local issues with certain criteria and band levels. This is corroborated by the challenges reported by the raters, which they mainly attributed to the complexities inherent in such an assessment. Applying Weir’s (2005) framework in a mixed-methods approach facilitated the interpretation of the quantitative findings and yielded insights into potential validity threads.

In this study, composites obtained through low-temperature carbonization of elastomeric matrix highly filled with graphite, carbon black and short carbon fibers were studied for the purpose of determining residual stresses at different scales using a combination of several complementary methods. The state-of-the-art techniques included X-ray stress analysis using the sin2⁡ψ method, the micro-ring-core technique via Focused Ion Beam milling and Digital Image Correlation (FIB-DIC), the contour method, the strain gauge method, and the hole drilling technique with digital laser speckle pattern interferometry (DLSPI). It was found that the contour method could not be used implemented for residual stress evaluation due to the low electrical conductivity of composite. Moreover, the DLSPI hole drilling method did not reveal any fringes indicating significant residual stress level exceeding a few MPa. The strain gauge method also revealed a narrow residual stress distribution with an average value of approximately zero. In contrast, the X-ray sin2⁡ψ method as well as FIB-DIC technique both returned values of about 150–250 MPa. A hierarchical model of the composite is proposed based on the Davidenkov Type I–II–III stress classification that provides an explanation of these observations.

During a nightmarishly sleepless night, neither the first nor last endured by the protagonist of Georges Perec's Un homme qui dort, there appears a passage which seems to summon a self-reflexive reading: 'Il devrait y avoir des textes à ce sujet, des textes sûrs, qui permettraient de faire face à ces situations, beaucoup plus fréquentes qu'on ne le croit généralement.' 1 The protagonist, a student in post-war Paris, is in the midst of a crisis that -as this article explores -might be termed depression.The self-reflexive reading would ask if Un homme qui dort fills the gap it here signals, if it is itself a 'texte sûr', an unequivocal text, sufficiently self-assured that it might reliably guide those facing similar situations.This is the sort of reading I will be undertaking here.Un homme qui dort is a text charged with the question of literature's therapeutic potential, one which has attracted a great deal of interest in recent years.The World Health Organization has published a review of the role of the arts (including literature) in improving health and well-being, 2 while 'bibliotherapists' including Régine Detambel in France and Ella Berthould and Susan Elderkin in the UK have been prescribing books to clients, and literary scholars have been exploring questions about literature's therapeutic potential and ambitions. 3 The present study intends to contribute to this ongoing discussion through its reading of Perec's unsure text, a text that problematizes the language and categories through which mental distress is apprehended, but

One-third of pediatric patients with osteosarcoma (OS) develop lung metastases (LM), which is the primary predictor of mortality. While current treatments of patients with localized bone disease have been successful in producing 5-year survival rates of 65–70%, patients with LM experience poor survival rates of only 19–30%. Unacceptably, this situation that has remained unchanged for 30 years. Thus, there is an urgent need to elucidate the mechanisms of metastatic spread in OS and to identify targetable molecular pathways that enable more effective treatments for patients with LM. We aimed to identify OS-specific gene alterations using RNA-sequencing of extremity and LM human tissues. Samples of extremity and LM tumors, including 4 matched sets, were obtained from patients with OS. Our data demonstrate aberrant regulation of the androgen receptor (AR) pathway in LM and predicts aldehyde dehydrogenase 1A1 (ALDH1A1) as a downstream target. Identification of AR pathway upregulation in human LM tissue samples may provide a target for novel therapeutics for patients with LM resistant to conventional chemotherapy.