2,953 results on '"P. O’Mahony"'
Search Results
2. Habit Coach: Customising RAG-based chatbots to support behavior change
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Arabi, Arian Fooroogh Mand, Koyuturk, Cansu, O'Mahony, Michael, Calati, Raffaella, and Ognibene, Dimitri
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Computer Science - Human-Computer Interaction ,Computer Science - Artificial Intelligence ,Computer Science - Computers and Society - Abstract
This paper presents the iterative development of Habit Coach, a GPT-based chatbot designed to support users in habit change through personalized interaction. Employing a user-centered design approach, we developed the chatbot using a Retrieval-Augmented Generation (RAG) system, which enables behavior personalization without retraining the underlying language model (GPT-4). The system leverages document retrieval and specialized prompts to tailor interactions, drawing from Cognitive Behavioral Therapy (CBT) and narrative therapy techniques. A key challenge in the development process was the difficulty of translating declarative knowledge into effective interaction behaviors. In the initial phase, the chatbot was provided with declarative knowledge about CBT via reference textbooks and high-level conversational goals. However, this approach resulted in imprecise and inefficient behavior, as the GPT model struggled to convert static information into dynamic and contextually appropriate interactions. This highlighted the limitations of relying solely on declarative knowledge to guide chatbot behavior, particularly in nuanced, therapeutic conversations. Over four iterations, we addressed this issue by gradually transitioning towards procedural knowledge, refining the chatbot's interaction strategies, and improving its overall effectiveness. In the final evaluation, 5 participants engaged with the chatbot over five consecutive days, receiving individualized CBT interventions. The Self-Report Habit Index (SRHI) was used to measure habit strength before and after the intervention, revealing a reduction in habit strength post-intervention. These results underscore the importance of procedural knowledge in driving effective, personalized behavior change support in RAG-based systems., Comment: Accepted for Italian Workshop on Artificial Intelligence for Human Machine Interaction (AIxHMI 2024), November 26, 2024, Bolzano, Italy
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- 2024
3. Towards Utilising a Range of Neural Activations for Comprehending Representational Associations
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O'Mahony, Laura, Nikolov, Nikola S., and O'Sullivan, David JP
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Computer Science - Computer Vision and Pattern Recognition ,Computer Science - Machine Learning - Abstract
Recent efforts to understand intermediate representations in deep neural networks have commonly attempted to label individual neurons and combinations of neurons that make up linear directions in the latent space by examining extremal neuron activations and the highest direction projections. In this paper, we show that this approach, although yielding a good approximation for many purposes, fails to capture valuable information about the behaviour of a representation. Neural network activations are generally dense, and so a more complex, but realistic scenario is that linear directions encode information at various levels of stimulation. We hypothesise that non-extremal level activations contain complex information worth investigating, such as statistical associations, and thus may be used to locate confounding human interpretable concepts. We explore the value of studying a range of neuron activations by taking the case of mid-level output neuron activations and demonstrate on a synthetic dataset how they can inform us about aspects of representations in the penultimate layer not evident through analysing maximal activations alone. We use our findings to develop a method to curate data from mid-range logit samples for retraining to mitigate spurious correlations, or confounding concepts in the penultimate layer, on real benchmark datasets. The success of our method exemplifies the utility of inspecting non-maximal activations to extract complex relationships learned by models., Comment: 18 pages, 11 figures
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- 2024
4. Learning Color Equivariant Representations
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O'Mahony, Felix, Yang, Yulong, and Allen-Blanchette, Christine
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Computer Science - Computer Vision and Pattern Recognition ,Computer Science - Machine Learning - Abstract
In this paper, we introduce group convolutional neural networks (GCNNs) equivariant to color variation. GCNNs have been designed for a variety of geometric transformations from 2D and 3D rotation groups, to semi-groups such as scale. Despite the improved interpretability, accuracy and generalizability of these architectures, GCNNs have seen limited application in the context of perceptual quantities. Notably, the recent CEConv network uses a GCNN to achieve equivariance to hue transformations by convolving input images with a hue rotated RGB filter. However, this approach leads to invalid RGB values which break equivariance and degrade performance. We resolve these issues with a lifting layer that transforms the input image directly, thereby circumventing the issue of invalid RGB values and improving equivariance error by over three orders of magnitude. Moreover, we extend the notion of color equivariance to include equivariance to saturation shift. Our hue-, saturation-, and color-equivariant networks achieve strong generalization to out-of-distribution perceptual variations and improved sample efficiency over conventional architectures. We demonstrate the utility of our approach on synthetic and real world datasets where we consistently outperform competitive baselines.
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- 2024
5. A Bayesian factor analysis model for high-dimensional microbiome count data
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Ba, Ismaïla, Turgeon, Maxime, Veniamin, Simona, Joel, Juan, Miller, Richard, Graham, Morag, Bonner, Christine, Bernstein, Charles N., Arnold, Douglas L., Bar-Or, Amit, Marrie, Ruth Ann, O'Mahony, Julia, Yeh, E. Ann, Banwell, Brenda, Waubant, Emmanuelle, Knox, Natalie, Van Domselaar, Gary, Mirza, Ali I., Armstrong, Heather, Muthukumarana, Saman, and McGregor, Kevin
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Statistics - Methodology - Abstract
Dimension reduction techniques are among the most essential analytical tools in the analysis of high-dimensional data. Generalized principal component analysis (PCA) is an extension to standard PCA that has been widely used to identify low-dimensional features in high-dimensional discrete data, such as binary, multi-category and count data. For microbiome count data in particular, the multinomial PCA is a natural counterpart of the standard PCA. However, this technique fails to account for the excessive number of zero values, which is frequently observed in microbiome count data. To allow for sparsity, zero-inflated multivariate distributions can be used. We propose a zero-inflated probabilistic PCA model for latent factor analysis. The proposed model is a fully Bayesian factor analysis technique that is appropriate for microbiome count data analysis. In addition, we use the mean-field-type variational family to approximate the marginal likelihood and develop a classification variational approximation algorithm to fit the model. We demonstrate the efficiency of our procedure for predictions based on the latent factors and the model parameters through simulation experiments, showcasing its superiority over competing methods. This efficiency is further illustrated with two real microbiome count datasets. The method is implemented in R., Comment: 2 figures, 3 tables
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- 2024
6. Pharmacological Pain Treatment in Older Persons
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Pickering, Gisèle, Kotlińska-Lemieszek, Aleksandra, Krcevski Skvarc, Nevenka, O’Mahony, Denis, Monacelli, Fiammetta, Knaggs, Roger, Morel, Véronique, and Kocot-Kępska, Magdalena
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- 2024
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7. Correction: The association between medication use and health-related quality of life in multimorbid older patients with polypharmacy
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Falke, Charlotte, Karapinar, Fatma, Bouvy, Marcel, Emmelot, Mariëlle, Belitser, Svetlana, Boland, Benoit, O’Mahony, Denis, Murphy, Kevin D., Haller, Moa, Salari, Paola, Schwenkglenks, Matthias, Rodondi, Nicolas, Egberts, Toine, and Knol, Wilma
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- 2024
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8. Irish national real-world analysis of the clinical and economic impact of 21-gene oncotype DX® testing in early-stage, 1-3 lymph node-positive, oestrogen receptor-positive, HER2-negative, breast cancer
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Browne, I. M., McLaughlin, R. A., Weadick, C. S., O’Sullivan, S., McSorley, L. M., Hadi, D. K., Millen, S. J., Higgins, M. J., Crown, J. P., Prichard, R. S., McCartan, D. P., Hill, A. DK., Connolly, R. M., Noonan, S. A., O’Mahony, D., Murray, C., O’Hanlon-Brown, C., Hennessy, B. T., Quinn, C. M., Kelly, C. M., O’Reilly, S., Morris, P. G., and Walshe, J. M.
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- 2024
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9. “Textbook outcome(s)” in colorectal surgery: a systematic review and meta-analysis
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Mac Curtain, Benjamin M., Qian, Wanyang, O’Mahony, Aaron, Deshwal, Avinash, Mac Curtain, Reuben D., Temperley, Hugo C., Sullivan, Niall O., and Ng, Zi Qin
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- 2024
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10. On the Detection of Anomalous or Out-Of-Distribution Data in Vision Models Using Statistical Techniques
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O'Mahony, Laura, O'Sullivan, David JP, and Nikolov, Nikola S.
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Computer Science - Computer Vision and Pattern Recognition ,Computer Science - Machine Learning - Abstract
Out-of-distribution data and anomalous inputs are vulnerabilities of machine learning systems today, often causing systems to make incorrect predictions. The diverse range of data on which these models are used makes detecting atypical inputs a difficult and important task. We assess a tool, Benford's law, as a method used to quantify the difference between real and corrupted inputs. We believe that in many settings, it could function as a filter for anomalous data points and for signalling out-of-distribution data. We hope to open a discussion on these applications and further areas where this technique is underexplored.
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- 2024
11. Demystifying Chains, Trees, and Graphs of Thoughts
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Besta, Maciej, Memedi, Florim, Zhang, Zhenyu, Gerstenberger, Robert, Piao, Guangyuan, Blach, Nils, Nyczyk, Piotr, Copik, Marcin, Kwaśniewski, Grzegorz, Müller, Jürgen, Gianinazzi, Lukas, Kubicek, Ales, Niewiadomski, Hubert, O'Mahony, Aidan, Mutlu, Onur, and Hoefler, Torsten
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Computer Science - Computation and Language ,Computer Science - Artificial Intelligence ,Computer Science - Machine Learning - Abstract
The field of natural language processing (NLP) has witnessed significant progress in recent years, with a notable focus on improving large language models' (LLM) performance through innovative prompting techniques. Among these, prompt engineering coupled with structures has emerged as a promising paradigm, with designs such as Chain-of-Thought, Tree of Thoughts, or Graph of Thoughts, in which the overall LLM reasoning is guided by a structure such as a graph. As illustrated with numerous examples, this paradigm significantly enhances the LLM's capability to solve numerous tasks, ranging from logical or mathematical reasoning to planning or creative writing. To facilitate the understanding of this growing field and pave the way for future developments, we devise a general blueprint for effective and efficient LLM reasoning schemes. For this, we conduct an in-depth analysis of the prompt execution pipeline, clarifying and clearly defining different concepts. We then build the first taxonomy of structure-enhanced LLM reasoning schemes. We focus on identifying fundamental classes of harnessed structures, and we analyze the representations of these structures, algorithms executed with these structures, and many others. We refer to these structures as reasoning topologies, because their representation becomes to a degree spatial, as they are contained within the LLM context. Our study compares existing prompting schemes using the proposed taxonomy, discussing how certain design choices lead to different patterns in performance and cost. We also outline theoretical underpinnings, relationships between prompting and other parts of the LLM ecosystem such as knowledge bases, and the associated research challenges. Our work will help to advance future prompt engineering techniques.
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- 2024
12. The US Organ Transplantation System: HRSA’s Modernization Initiative
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Adashi, Eli Y. and O’Mahony, Daniel P.
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- 2024
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13. A Practical Approach to Tailor the Term Long COVID for Diagnostics, Therapy and Epidemiological Research for Improved Long COVID Patient Care
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Hoffmann, Kathryn, Stingl, Michael, O’Mahony, Liam, and Untersmayr, Eva
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- 2024
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14. The association between medication use and health-related quality of life in multimorbid older patients with polypharmacy
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Falke, Charlotte, Karapinar, Fatma, Bouvy, Marcel, Emmelot, Mariëlle, Belitser, Svetlana, Boland, Benoit, O’Mahony, Denis, Murphy, Kevin D., Haller, Moa, Salari, Paola, Schwenkglenks, Matthias, Rodondi, Nicolas, Egberts, Toine, and Knol, Wilma
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- 2024
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15. Economic cost-benefit analysis of person-centred medicines reviews by general practice pharmacists
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O’Mahony, Cian, Dalton, Kieran, O’Hagan, Leon, Murphy, Kevin D., Kinahan, Clare, Coyle, Emma, Sahm, Laura J., Byrne, Stephen, and Kirke, Ciara
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- 2024
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16. Beyond the Buzz: Scholarly Approaches to the Study of Work
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Monteiro, Pedro, Nicolini, Davide, Erickson, Ingrid, Cohen, Lisa E, Dokko, Gina, Corporaal, Greetje F, Karunakaran, Arvind, Bechky, Beth A, and O’Mahony, Siobhan
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Commerce ,Management ,Tourism and Services ,Strategy ,Management and Organisational Behaviour ,work ,job analysis or job design ,organization theory ,careers ,technology ,occupations ,Business and Management ,Business & Management ,Strategy ,management and organisational behaviour - Abstract
The place of work in organization studies and management has waxed and waned. Yet, today, social and technological developments have raised again interest in the study of work and this curated discussion brings together experts in key approaches to this topic. Seven contributions have been selected to provide a panorama of what we know about work while pointing to some uncharted territories worthy of future exploration. The contributions outline the principles behind and value of systemic, contextualized, or holistic view of work and report insights on how changes in some work components reverberate in its broader ecology. We hope this curated discussion will make us more aware of the collective journey scholars have charted so far while posing new questions and opening or re-directing new avenues of inquiry.
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- 2024
17. A cross-sectional study of the relative availability and prominence of shelf space allocated to healthy and unhealthy foods in supermarkets in urban Ireland, by area-level deprivation
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O’Mahony, S., Collins, N., Doyle, G., McCann, A., Burke, K., Moore, A., and Gibney, E. R.
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- 2024
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18. The feasibility and usability of mixed reality teaching in a hospital setting based on self-reported perceptions of medical students
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Johnston, Michael, O’Mahony, Megan, O’Brien, Niall, Connolly, Murray, Iohom, Gabriella, Kamal, Mohsin, Shehata, Ahmed, and Shorten, George
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- 2024
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19. The gut microbiota in persistent post-operative pain following breast cancer surgery
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Masaud, Khaled, Collins, James M., Rubio, Raul Cabrera, Corrigan, Mark, Cotter, Paul D., O’Brien, Niall, Bluett, Ronan, Jimenez, Clare Keaveney, O’Mahony, Siobhain M., and Shorten, George D.
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- 2024
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20. The trials and errors of developing an experimental model to study the impact of maternal gut microbiome disruption on perinatal asphyxia
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Mara Ioana Ionescu, Ana Maria Catrina, Ioana Alexandra Dogaru, Didina Catalina Barbalata, Cristian Ciotei, Cerasela Haidoiu, Vladimir Suhaianu, Gratiela Gradisteanu Pircalabioru, Siobhain M. O’Mahony, and Ana-Maria Zagrean
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gestational antibiotic administration ,gut-brain axis ,maternal gut microbiome ,neurodevelopment ,perinatal asphyxia ,Reproduction ,QH471-489 ,Gynecology and obstetrics ,RG1-991 - Abstract
Maternal gut microbiome impairment has garnered attention for its potential role in influencing neurodevelopmental outcomes in offspring, especially in situations that increase brain vulnerability such as perinatal asphyxia (PA). Maternal microbiome and fetal brain interplay emerge as a critical link between maternal health and offspring neurodevelopment. This study aims to generate a model to assess the impact of maternal dysbiosis triggered by gestational antibiotic administration and PA on offspring neurodevelopment. Wistar rats were subjected to antibiotics in drinking water from the 11th gestational day until birth. On the 6th postnatal day, pups were subjected to PA/normoxia, resulting in four experimental groups: control-normoxia, antibiotics-normoxia, control-asphyxia, and antibiotics-asphyxia. Early-life behavioral tests were conducted between postnatal days 7 and 9. The initial antimicrobial cocktail (ampicillin, vancomycin, neomycin, clindamycin, amphotericin-B) led to an increased number of miscarriages, poor weight gain during pregnancy, reduced offspring weight, and changes in the maternal gut microbiome compared to control. Offspring presented impaired neurodevelopmental reflexes in both PA and antibiotic groups and increased hippocampal neuroinflammation. Due to these detrimental effects, a more pregnancy-safe antibiotic cocktail was used for a second experiment (ampicillin, vancomycin, neomycin, meropenem). This resulted in no miscarriages or pregnancy-weight loss but was still linked to gut microbiome disruption. PA impaired neurodevelopmental reflexes and increased neuroinflammation, effects amplified by antibiotic administration. These preliminary findings reveal the cumulative potential of maternal dysbiosis and PA on neurodevelopment impairment, emphasizing caution in gestational antimicrobial use. Further investigations should include offspring long-term follow-up and maternal behavior and integrate probiotics to counteract antibiotic effects.
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- 2024
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21. A cross-sectional study of the relative availability and prominence of shelf space allocated to healthy and unhealthy foods in supermarkets in urban Ireland, by area-level deprivation
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S. O’Mahony, N. Collins, G. Doyle, A. McCann, K. Burke, A. Moore, and E. R. Gibney
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Retail food environment ,Supermarket ,Unhealthy food availability ,Unhealthy food visibility ,Area-level deprivation ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Diet-related noncommunicable diseases (NCDs) are a leading cause of ill-health and death across Europe. In Ireland, dietary intakes of saturated fat, free sugar and salt exceed World Health Organization recommendations, and excess consumption follows a social gradient increasing population risk of diet-related NCDs. The retail food environment can influence consumer food choice and subsequent dietary intakes. In high income countries, supermarkets are an increasingly influential actor in consumer food availability, choice, purchase, and subsequent food intake. This study aims to assess the relative availability and prominence of healthy and unhealthy foods in Irish supermarkets, by area-level deprivation. Methods This study used a cross-sectional study design, and applied a validated measure, as described in the INFORMAS Protocol: Food Retail – Food availability in supermarkets. Between October 2021 and February 2022, shelf space (m2) (height or depth (cm) × length (cm)) and prominence (visibility), of foods, classified as healthy and unhealthy and represented by a proxy indicator, were collected in supermarkets (n = 36) in County Dublin, Ireland. Overall the proportion of mean relative shelf space (m2), allocated to healthy and unhealthy foods, and its prominence, by area-level deprivation, and retailer, were determined. We used t-tests and one-way ANOVA to analyse possible differences between the proportion of relative shelf space available to healthy and unhealthy foods, and its prominence, by area-level deprivation and retailer. Results The study found the proportion of shelf space measured allocated to unhealthy food was 68.0% (SD 10.6). Unhealthy foods were more likely to be in areas of high prominence. Overall, there was no statistically significant difference between the proportion of relative shelf space available to unhealthy foods in areas of high and low deprivation. A statistically significant difference in the proportion of relative shelf space allocated to healthy and unhealthy food by area level deprivation was found in one retailer. Conclusion Unhealthy foods had a higher proportion of shelf space and were more prominent than healthy foods in supermarkets in County Dublin, Ireland. The current availability and prominence of foods in supermarkets does not align with Food Based Dietary Guideline recommendations and does not support consumers to make healthier food choices. There is a need for supermarkets in Ireland to improve the availability and prominence of healthy foods to support consumers to make healthier food choices.
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- 2024
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22. An analysis on the effects of speaker embedding choice in non auto-regressive TTS
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Stan, Adriana and O'Mahony, Johannah
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Electrical Engineering and Systems Science - Audio and Speech Processing ,Computer Science - Artificial Intelligence - Abstract
In this paper we introduce a first attempt on understanding how a non-autoregressive factorised multi-speaker speech synthesis architecture exploits the information present in different speaker embedding sets. We analyse if jointly learning the representations, and initialising them from pretrained models determine any quality improvements for target speaker identities. In a separate analysis, we investigate how the different sets of embeddings impact the network's core speech abstraction (i.e. zero conditioned) in terms of speaker identity and representation learning. We show that, regardless of the used set of embeddings and learning strategy, the network can handle various speaker identities equally well, with barely noticeable variations in speech output quality, and that speaker leakage within the core structure of the synthesis system is inevitable in the standard training procedures adopted thus far., Comment: Accepted for publication at ISCA Speech Synthesis Workshop 2023
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- 2023
23. Comparison of ‘Complete Anatomy’ (CA) to conventional methods for teaching laryngeal anatomy to first-year dental and dental hygiene students in Ireland
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Sarah Alturkustani, Sinead Mary Ryan, Siobhain M. O’Mahony, André Toulouse, Conor O'Mahony, and Mutahira Lone
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3D learning ,3D visualisation ,Anatomy education ,Dental education ,Larynx ,Technology-enhanced learning ,Human anatomy ,QM1-695 - Abstract
Background: Digital 3D visualisation tools have been increasingly used to supplement anatomy teaching with positive results reported in knowledge acquisition, 3D spatial understanding, and active student engagement. Despite their well-documented benefits, evidence of their learning effect on head and neck anatomy is limited. Methods: This cross-over design study aimed to compare using Complete Anatomy (CA) and conventional methods (prosections and plastic models) to learn laryngeal anatomy. Fifty-four first-year dental and dental hygiene students were randomly assigned to a CA and a conventional group. Pre- and post-tests were used to compare groups' knowledge gains, and a feedback questionnaire was used to compare students' perceptions towards CA. Results: Both groups improved significantly in the post-test compared to the pre-test (Cohen's d ≥ 0.8). The conventional group significantly outperformed their counterparts in total (Cohen's d = 0.57) and written questions (Cohen's d = 0.9). However, both groups performed equally in the identification questions. Question-based analysis shows that the CA group performed significantly better in the identification questions than in the written questions (Cohen's d = 0.51). Nearly half the students perceived the CA application as easy to use, and the same proportion believed CA assisted their learning of laryngeal anatomy. Conclusion: This study provides further evidence of the effectiveness of CA in knowledge gain and anatomical recognition and supports its use as supplementary to anatomy education in general and head and neck anatomy in particular.
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- 2024
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24. Antipsychotic prescribing and drug-related readmissions in multimorbid older inpatients: a post-hoc analysis of the OPERAM population
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Bienfait, A., Lagreula, J., Blum, M. R., Rodondi, N., Sallevelt, B. T. G. M., Knol, W., O’Mahony, D., Spinewine, A., Boland, B., and Dalleur, O.
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- 2024
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25. Do cognitive abilities reduce eyewitness susceptibility to the misinformation effect? A systematic review
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Brassil, Maryanne, O’Mahony, Cian, and Greene, Ciara M.
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- 2024
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26. Discovery of orbital ordering in Bi2Sr2CaCu2O8+x
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Wang, Shuqiu, Kennedy, Niall, Fujita, Kazuhiro, Uchida, Shin-ichi, Eisaki, Hiroshi, Johnson, Peter D., Davis, J. C. Séamus, and O’Mahony, Shane M.
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- 2024
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27. Response to letter by Masse O et al. STOPP/START version 3: clinical pharmacists are raising alarms
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O’Mahony, Denis, Cherubini, Antonio, Guiteras, Anna Renom, Denkinger, Michael, Beuscart, Jean-Baptiste, Onder, Graziano, Gudmundsson, Adalsteinn, Cruz-Jentoft, Alfonso J., Knol, Wilma, Bahat, Gülistan, van der Velde, Nathalie, Petrovic, Mirko, and Curtin, Denis
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- 2024
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28. Incisional hernias post renal transplant: a systematic review and meta-analysis
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Mac Curtain, B. M., Qian, W., Temperley, H. C., O’Mahony, A., Ng, Z. Q., and He, B.
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- 2024
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29. Two years of COVID-19 outbreaks in residential care facilities: quantifying workload impact of outbreak control activities on a regional public health team in Ireland, March 2020 to March 2022
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Carey, Cian, O’Sullivan, Margaret, O’Mahony, Mary, Sheahan, Anne, and Barrett, Peter
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- 2024
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30. What does BERT learn about prosody?
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Kakouros, Sofoklis and O'Mahony, Johannah
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Computer Science - Computation and Language - Abstract
Language models have become nearly ubiquitous in natural language processing applications achieving state-of-the-art results in many tasks including prosody. As the model design does not define predetermined linguistic targets during training but rather aims at learning generalized representations of the language, analyzing and interpreting the representations that models implicitly capture is important in bridging the gap between interpretability and model performance. Several studies have explored the linguistic information that models capture providing some insights on their representational capacity. However, the current studies have not explored whether prosody is part of the structural information of the language that models learn. In this work, we perform a series of experiments on BERT probing the representations captured at different layers. Our results show that information about prosodic prominence spans across many layers but is mostly focused in middle layers suggesting that BERT relies mostly on syntactic and semantic information., Comment: Accepted at the International Congress of Phonetic Sciences (ICPhS 2023; https://www.icphs2023.org/)
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- 2023
31. Disentangling Neuron Representations with Concept Vectors
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O'Mahony, Laura, Andrearczyk, Vincent, Muller, Henning, and Graziani, Mara
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Computer Science - Computer Vision and Pattern Recognition ,Computer Science - Machine Learning - Abstract
Mechanistic interpretability aims to understand how models store representations by breaking down neural networks into interpretable units. However, the occurrence of polysemantic neurons, or neurons that respond to multiple unrelated features, makes interpreting individual neurons challenging. This has led to the search for meaningful vectors, known as concept vectors, in activation space instead of individual neurons. The main contribution of this paper is a method to disentangle polysemantic neurons into concept vectors encapsulating distinct features. Our method can search for fine-grained concepts according to the user's desired level of concept separation. The analysis shows that polysemantic neurons can be disentangled into directions consisting of linear combinations of neurons. Our evaluations show that the concept vectors found encode coherent, human-understandable features.
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- 2023
32. A Practical Approach to Tailor the Term Long COVID for Diagnostics, Therapy and Epidemiological Research for Improved Long COVID Patient Care
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Kathryn Hoffmann, Michael Stingl, Liam O’Mahony, and Eva Untersmayr
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Long-COVID ,Definition ,Epidemiological research ,Clinical coding ,Diagnostics ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract The term long COVID (LC) effectively describes the broad long-term disease burden of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections, encompassing individual suffering and significant socioeconomic impacts. However, its general use hampers precise epidemiological research, diagnostics and therapeutic strategies. Misinterpretations occur, for example, when population surveys are compared to studies using health record data, because both refer to these data as LC. This also emphasizes the need for different terminology. The National Institute for Health and Care Excellence (NICE) rapid guideline differentiates ongoing symptomatic COVID-19 from post-COVID conditions, yet real-world observations challenge these two subgroup definitions. We propose refining the term LC into three subgroups: ongoing symptomatic COVID-19, SARS-CoV-2 induced or exacerbated diseases and post-acute COVID condition. This stratification aids targeted diagnostics, treatment and epidemiological research. Subgroup-specific documentation using the International Classification of Diseases, Tenth Revision (ICD-10) codes ensures accurate tracking and understanding of long-term effects. The subgroup of post-acute COVID condition again includes various symptoms, syndromes and diseases like post-exertional malaise (PEM), dysautonomia or cognitive dysfunctions. In this regard, differentiation, especially considering PEM, is crucial for effective diagnostics and treatment.
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- 2024
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33. Emergence of rifampicin-resistant staphylococci on the skin and nose of rifampicin-treated patients with an orthopaedic-device-related infection
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A. Wallimann, Y. Achermann, C. Ferris, M. Morgenstern, M. Clauss, V. Stadelmann, H. A. Rüdiger, L. O'Mahony, and T. F. Moriarty
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Orthopedic surgery ,RD701-811 - Abstract
Rifampicin is a key antibiotic in the treatment of staphylococcal biofilm infections. In this pilot study, we found that patients who received rifampicin for treatment of an orthopaedic-device-related infection (ODRI) were colonized with rifampicin-resistant staphylococci during treatment and this persisted for up to 2 months after cessation of treatment.
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- 2024
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34. Mediterranean diet and associations with the gut microbiota and pediatric-onset multiple sclerosis using trivariate analysis
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Ali I. Mirza, Feng Zhu, Natalie Knox, Lucinda J. Black, Alison Daly, Christine Bonner, Gary Van Domselaar, Charles N. Bernstein, Ruth Ann Marrie, Janace Hart, E. Ann Yeh, Amit Bar-Or, Julia O’Mahony, Yinshan Zhao, William Hsiao, Brenda Banwell, Emmanuelle Waubant, and Helen Tremlett
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Medicine - Abstract
Abstract Background The interplay between diet and the gut microbiota in multiple sclerosis (MS) is poorly understood. We aimed to assess the interrelationship between diet, the gut microbiota, and MS. Methods We conducted a case-control study including 95 participants (44 pediatric-onset MS cases, 51 unaffected controls) enrolled from the Canadian Pediatric Demyelinating Disease Network study. All had completed a food frequency questionnaire ≤21-years of age, and 59 also provided a stool sample. Results Here we show that a 1-point increase in a Mediterranean diet score is associated with 37% reduced MS odds (95%CI: 10%–53%). Higher fiber and iron intakes are also associated with reduced MS odds. Diet, not MS, explains inter-individual gut microbiota variation. Several gut microbes abundances are associated with both the Mediterranean diet score and having MS, and these microbes are potential mediators of the protective associations of a healthier diet. Conclusions Our findings suggest that the potential interaction between diet and the gut microbiota is relevant in MS.
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- 2024
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35. A Likelihood Ratio Approach for Utilizing Case‐Control Data in the Clinical Classification of Rare Sequence Variants: Application to BRCA1 and BRCA2
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Zanti, Maria, O′Mahony, Denise G, Parsons, Michael T, Li, Hongyan, Dennis, Joe, Aittomäkkiki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Aronson, Kristan J, Augustinsson, Annelie, Becher, Heiko, Bojesen, Stig E, Bolla, Manjeet K, Brenner, Hermann, Brown, Melissa A, Buys, Saundra S, Canzian, Federico, Caputo, Sandrine M, Castelao, Jose E, Chang-Claude, Jenny, Collaborators, GC-HBOC study, Czene, Kamila, Daly, Mary B, De Nicolo, Arcangela, Devilee, Peter, Dörk, Thilo, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Engel, Christoph, Evans, D Gareth, Fasching, Peter A, Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A, Gentry-Maharaj, Aleksandra, Giele, Willemina RR Geurts-, Giles, Graham G, Glendon, Gord, Goldberg, Mark S, Garcia, Encarna B Gómez, Güendert, Melanie, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A, Hall, Per, Hamann, Ute, Harkness, Elaine F, Hogervorst, Frans BL, Hollestelle, Antoinette, Hoppe, Reiner, Hopper, John L, Houdayer, Claude, Houlston, Richard S, Howell, Anthony, Investigators, ABCTB, Jakimovska, Milena, Jakubowska, Anna, Jernström, Helena, John, Esther M, Kaaks, Rudolf, Kitahara, Cari M, Koutros, Stella, Kraft, Peter, Kristensen, Vessela N, Lacey, James V, Lambrechts, Diether, Léoné, Melanie, Lindblom, Annika, Lubiński, Jan, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Menon, Usha, Milne, Roger L, Monteiro, Alvaro N, Murphy, Rachel A, Neuhausen, Susan L, Nevanlinna, Heli, Newman, William G, Offit, Kenneth, Park, Sue K, James, Paul, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Punie, Kevin, Radice, Paolo, Rashid, Muhammad U, Rennert, Gad, Romero, Atocha, Rosenberg, Efraim H, Saloustros, Emmanouil, Sandler, Dale P, Schmidt, Marjanka K, Schmutzler, Rita K, and Shu, Xiao-Ou
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Biological Sciences ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Genetics ,Biotechnology ,Genetic Testing ,Prevention ,Cancer ,Human Genome ,Women's Health ,Breast Cancer ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Humans ,Case-Control Studies ,BRCA2 Protein ,Genetic Predisposition to Disease ,Female ,BRCA1 Protein ,Breast Neoplasms ,Likelihood Functions ,Genetic Variation ,Penetrance ,GC-HBOC study Collaborators ,ABCTB Investigators ,ACMG/AMP ,BRCA ,PS4 ,VUS ,case-control ,likelihood ratio ,variant classification ,Clinical Sciences ,Genetics & Heredity ,Clinical sciences - Abstract
A large number of variants identified through clinical genetic testing in disease susceptibility genes, are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion), can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analyses of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC), and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity - findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared to classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and pre-formatted excel calculators for implementation of the method for rare variants in BRCA1, BRCA2 and other high-risk genes with known penetrance.
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- 2023
36. Discovery of Orbital Ordering in Bi2Sr2CaCu2O8+x
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Wang, Shuqiu, Kennedy, Niall, Fujita, Kazuhiro, Uchida, Shin-ichi, Eisaki, Hiroshi, Johnson, Peter D., Davis, J. C. Séamus, and O'Mahony, Shane M.
- Subjects
Condensed Matter - Superconductivity ,Condensed Matter - Strongly Correlated Electrons - Abstract
The primordial ingredient of cuprate superconductivity is the CuO2 unit cell. Here, theoretical attention usually concentrates on the intra-atom Coulombic interactions dominating the 3d^9 and 3d^10 configurations of each copper ion. However, if Coulombic interactions also occur between electrons of the 2p^6 orbitals of each planar oxygen atom, spontaneous orbital ordering may split their energy levels. This long predicted intra-unit cell symmetry breaking should then generate an orbital ordered phase, for which the charge-transfer energy E separating the 2p^6 and 3d^10orbitals is distinct for the two oxygen atoms. Here we introduce sublattice resolved E(r) imaging techniques to CuO2 studies and discover intra-unit-cell rotational symmetry breaking of E(r), with energy-level splitting between the two oxygen atoms on the 50 meV scale. Spatially, this state is arranged in disordered Ising domains of orthogonally oriented orbital order that appear bounded by dopant ions, and within whose domain walls low energy electronic quadrupolar two-level systems occur. Overall, these data reveal a Q=0 orbitally ordered state that splits the energy levels of the oxygen orbitals by ~50 meV, in underdoped CuO2., Comment: Manuscript: 21 pages, 4 figures. Methods: 40 pages, 23 figures
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- 2023
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37. More than just a number: the gut microbiota and brain function across the extremes of life
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Nathan D. Nuzum, Clara Deady, Sarah Kittel-Schneider, John F. Cryan, Siobhain M. O'Mahony, and Gerard Clarke
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Neurodevelopment ,neurodegeneration ,gut bacteria ,gut-brain-axis ,early-life ,older adult ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Understanding the interrelationship between the gut microbiota and host physiology, although still in its relative infancy, has taken important steps forward over the past decade. In the context of brain disorders including those characterized by neurodevelopmental and neurodegenerative changes there have been important advances. However, initially research involved correlational analyses, had limited translational scope, and lacked functional assessments. Thus, largescale longitudinal clinical investigations that assess causation and underlying mechanisms via in depth analysis methods are needed. In neurodegeneration research, strong causal evidence now links the gut microbiome to Alzheimer's (AD), and Parkinson's Disease (PD), as supported by human-to-animal transplantation studies. Longitudinal interventions are being conducted in AD, PD, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Neurodevelopmental research has also seen a boon in microbiome-related clinical research including in autism, Attention-deficit/hyperactivity disorder, and schizophrenia, which is confirming prior animal model work regarding the key time-windows in the gut microbiome important for infant cognition. While recent research advances represent important progress, fundamental knowledge gaps and obstacles remain. Knowing how and why the gut microbiome changes at the extremes of life will develop our mechanistic understanding and help build the evidence base as we strive toward counteracting microbial missteps with precision therapeutic interventions.
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- 2024
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38. Dysrupted microbial tryptophan metabolism associates with SARS-CoV-2 acute inflammatory responses and long COVID
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Lu Yao, Hannah Devotta, Junhui Li, Nonhlanhla Lunjani, Corinna Sadlier, Aonghus Lavelle, Werner C. Albrich, Jens Walter, Paul W. O’Toole, and Liam O’Mahony
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Microbiota ,COVID-19 ,tryptophan ,indoles ,long COVID ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and risk of long COVID has been associated with the depletion or over-abundance of specific taxa within the gut microbiome. However, the microbial mechanisms mediating these effects are not yet known. We hypothesized that altered microbial production of tryptophan and its downstream derivatives might contribute to inappropriate immune responses to viral infection. In patients hospitalized with COVID-19 (n = 172), serum levels of tryptophan and indole-3-propionate (IPA) negatively correlated with serum levels of many proinflammatory mediators (including C-reactive protein and Serum amyloid A), while C-glycosyltryptophan (C-Trp), indole-3-lactic acid (ILA) and indole-3-acetic acid (IAA) levels were positively correlated with levels of acute phase proteins, proinflammatory cytokines, alarmins and chemokines. A similar pattern was observed in long COVID patients (n = 20) where tryptophan and IPA were negatively associated with a large number of serum cytokines, while C-Trp and IAA were positively associated with circulating cytokine levels. Metagenomic analysis of the fecal microbiota showed the relative abundance of genes encoding the microbial enzymes required for tryptophan production (e.g. anthranilate synthase) and microbial tryptophan metabolism was significantly lower in patients hospitalized with COVID-19 (n = 380) compared to healthy controls (n = 270). Microbial tryptophan metabolites reduced innate cell proinflammatory responses to cytosolic DNA sensor Stimulator of interferon genes (STING), toll-like receptor (TLR)-3 and TLR-4 stimulation in vitro, while IL-10 secretion was enhanced. Microbial tryptophan metabolites also modified ex vivo human lymphocyte responses by limiting the production of TH1 and TH17 associated cytokines, while enhancing secretion of IL-22. These data suggest that lower levels of tryptophan production and tryptophan metabolism by gut microbes may increase the risk of severe and chronic outcomes to SARS-CoV-2 infection due to impaired innate and adaptive responses to infection. Screening patients for lower-level microbiome capacity for tryptophan metabolism may help identify at-risk individuals.
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- 2024
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39. Gut microbial metabolic signatures in diabetes mellitus and potential preventive and therapeutic applications
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Enriqueta Garcia-Gutierrez, A. Kate O’Mahony, Reinaldo Sousa Dos Santos, Laura Marroquí, and Paul D. Cotter
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Type 1 diabetes ,type 2 diabetes ,gestational diabetes ,gut microbiota ,gut barrier ,gut dysbiosis ,Diseases of the digestive system. Gastroenterology ,RC799-869 - Abstract
Diabetes mellitus can be subdivided into several categories based on origin and clinical characteristics. The most common forms of diabetes are type 1 (T1D), type 2 diabetes (T2D) and gestational diabetes mellitus (GDM). T1D and T2D are chronic diseases affecting around 537 million adults worldwide and it is projected that these numbers will increase by 12% over the next two decades, while GDM affects up to 30% of women during pregnancy, depending on diagnosis methods. These forms of diabetes have varied origins: T1D is an autoimmune disease, while T2D is commonly associated with, but not limited to, certain lifestyle patterns and GDM can result of a combination of genetic predisposition and pregnancy factors. Despite some pathogenic differences among these forms of diabetes, there are some common markers associated with their development. For instance, gut barrier impairment and inflammation associated with an unbalanced gut microbiota and their metabolites may be common factors in diabetes development and progression. Here, we summarize the microbial signatures that have been linked to diabetes, how they are connected to diet and, ultimately, the impact on metabolite profiles resulting from host-gut microbiota-diet interactions. Additionally, we summarize recent advances relating to promising preventive and therapeutic interventions focusing on the targeted modulation of the gut microbiota to alleviate T1D, T2D and GDM.
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- 2024
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40. Demystifying Open Science in health psychology and behavioral medicine: a practical guide to Registered Reports and Data Notes
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Emma Norris, Aoife O’Mahony, Rory Coyne, Tugce Varol, James A. Green, James Reynolds, and Elaine Toomey
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Open Science ,Open Scholarship ,Open Research ,Registered Reports ,Data Notes ,Health Psychology ,Medicine ,Psychology ,BF1-990 - Abstract
Open Science practices are integral to increasing transparency, reproducibility, and accessibility of research in health psychology and behavioral medicine. Drives to facilitate Open Science practices are becoming increasingly evident in journal editorial policies, including the establishment of new paper formats such as Registered Reports and Data Notes. This paper provides: (i) an overview of the current state of Open Science policies within health psychology and behavioral medicine, (ii) a call for submissions to an Article Collection of Registered Reports and Data Notes as new paper formats within the journal of Health Psychology & Behavioral Medicine, (iii) an overview of Registered Reports and Data Notes, and (iv) practical considerations for authors and reviewers of Registered Reports and Data Notes.
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- 2024
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41. 'People want better': a qualitative exploration of stakeholders’ views on introducing well-being coordinators in the screen industry
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John Goodwin, Eleanor McSherry, Ryan Goulding, James O’Mahony, Rachael O’Callaghan, and Ciara Chambers
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creative industry ,film ,tv ,interpretive description ,mental health ,qualitative ,screen industry ,well-being ,Medicine (General) ,R5-920 - Abstract
Purpose There are several factors that negatively impact the well-being of those working in the screen industry. Consequently, the need to introduce Well-being Coordinators has been identified. This study explored the experiences of participants who undertook a Well-being Coordination course tailored for the screen sector. Additionally, it sought to delve into perspectives regarding well-being within the screen industry. Methods Semi-structured interviews were conducted. The study was guided by an interpretive descriptive approach. Reflexive thematic analysis was used to analyse data. Findings Five themes were identified: Opportunities and challenges working in the screen industry, co-existing with harassment, the need for change: importance of wellbeing, becoming a well-being co-ordinator: learning from the course, and the future of the well-being co-ordinator role: opportunities and challenges. The reality that cast and crew co-exist with several forms of harassment within the industry was noted. Despite this, there is hope for the future of the screen sector, particularly the positive impact the role of the Well-being Coordinator could have. Conclusions The experiences of professionals across the screen industry vary; however, a pervasive culture of bullying and harassment is commonplace. Through the introduction of Well-being Coordinators, there is the potential to enact positive change.
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- 2024
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42. Sex specific gut-microbiota signatures of resilient and comorbid gut-brain phenotypes induced by early life stress
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Lars Wilmes, Valentina Caputi, Thomaz F.S. Bastiaanssen, James M. Collins, Fiona Crispie, Paul D. Cotter, Timothy G. Dinan, John F. Cryan, Gerard Clarke, and Siobhain M. O'Mahony
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Visceral pain ,Microbiota ,Psychiatric comorbidities ,Sex differences ,Early life stress ,IBS ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 ,Neurology. Diseases of the nervous system ,RC346-429 ,Neurophysiology and neuropsychology ,QP351-495 - Abstract
Background: Alterations in gut-brain axis communication pathways and the gut microbiota ecosystem caused by early life stress have been extensively described as critical players in the pathophysiology of stress-induced disorders. However, the extent to which stress-induced gut microbiota alterations manifest in early life and contribute to the sex-specific susceptibility to distinct gut-brain phenotypes in adulthood has yet to be defined. Methods: Male and female Sprague-Dawley rat offspring underwent maternal separation (3h/day from postnatal day 2–12). Faecal samples were collected before weaning for gut microbiota 16S rRNA sequencing and metabolomic analysis. Visceral pain sensitivity and negative valence behaviours were assessed in adulthood using colorectal distension and the forced swim test respectively. Behavioural data were processed in a two-step cluster analysis to identify groupings within the dataset. Multi-omics analysis was carried out to investigate if the microbial signatures following early life stress were already defined according to the membership of the adult behavioural phenotypes. Results: Maternal separation resulted in increased visceral hypersensitivity while showing a trend for a sex-dependent increase in negative valence behaviour in adulthood. The cluster analysis revealed four clusters within the dataset representing distinct pathophysiological domains reminiscent of the behavioural consequences of early-life stress: 1. resilient, 2. pain, 3. immobile and 4. comorbid. The early life gut microbiota of each of these clusters show distinct alterations in terms of diversity, genus level differential abundance, and functional modules. Multi-omic integrations points towards a role for different metabolic pathways underlying each cluster-specific phenotype. Conclusion: Our study is the first to identify distinct phenotypes defined by susceptibility or resilience to gut-brain dysfunction induced by early life stress. The gut microbiota in early life shows sex-dependent alterations in each cluster that precede specific behavioural phenotypes in adulthood. Future research is warranted to determine the causal relationship between early-life stress-induced changes in the gut microbiota and to understand the trajectory leading to the manifestation of different behavioural phenotypes in adulthood.
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- 2024
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43. Biodielectrics: old wine in a new bottle?
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Hema Dinesh Barnana, Syed A. M. Tofail, Krittish Roy, Charlie O’Mahony, Veronika Hidaši Turiničová, Maroš Gregor, and Ehtsham ul Haq
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Biodielectrics ,Biopiezoelectrics ,Biopyroelectrics ,Bioferroelectrics ,low k dielectrics ,Pieoelectrics ,Biotechnology ,TP248.13-248.65 - Abstract
Biodielectrics is a subset of biological and/or bioinspired materials that has brought a huge transformation in the advancement of medical science, such as localized drug delivery in cancer therapeutics, health monitoring, bone and nerve repair, tissue engineering and use in other nanoelectromechanical systems (NEMS). While biodielectrics has long been used in the field of electrical insulation for over a century, polar dielectric properties of biological building blocks have not been well understood at the fundamental building block level. In this review article, we provide a brief overview of dielectric properties of biological building blocks and its hierarchical organisations to include polar dielectric properties such as piezo, pyro, and ferroelectricity. This review article also discusses recent trends, scope, and potential applications of these dielectrics in science and technology. We highlight electromechanical properties embedded in rationally designed organic assemblies, and the challenges and opportunities inherent in mapping from molecular amino acid building blocks to macroscopic analogs of biological fibers and tissues, in pursuit of sustainable materials for next-generation technologies.
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- 2024
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44. Ovarian cancer pathology characteristics as predictors of variant pathogenicity in BRCA1 and BRCA2
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O’Mahony, Denise G, Ramus, Susan J, Southey, Melissa C, Meagher, Nicola S, Hadjisavvas, Andreas, John, Esther M, Hamann, Ute, Imyanitov, Evgeny N, Andrulis, Irene L, Sharma, Priyanka, Daly, Mary B, Hake, Christopher R, Weitzel, Jeffrey N, Jakubowska, Anna, Godwin, Andrew K, Arason, Adalgeir, Bane, Anita, Simard, Jacques, Soucy, Penny, Caligo, Maria A, Mai, Phuong L, Claes, Kathleen BM, Teixeira, Manuel R, Chung, Wendy K, Lazaro, Conxi, Hulick, Peter J, Toland, Amanda E, Pedersen, Inge Sokilde, Neuhausen, Susan L, Vega, Ana, de la Hoya, Miguel, Nevanlinna, Heli, Dhawan, Mallika, Zampiga, Valentina, Danesi, Rita, Varesco, Liliana, Gismondi, Viviana, Vellone, Valerio Gaetano, James, Paul A, Janavicius, Ramunas, Nikitina-Zake, Liene, Nielsen, Finn Cilius, van Overeem Hansen, Thomas, Pejovic, Tanja, Borg, Ake, Rantala, Johanna, Offit, Kenneth, Montagna, Marco, Nathanson, Katherine L, Domchek, Susan M, Osorio, Ana, García, María J, Karlan, Beth Y, De Fazio, Anna, Bowtell, David, McGuffog, Lesley, Leslie, Goska, Parsons, Michael T, Dörk, Thilo, Speith, Lisa-Marie, dos Santos, Elizabeth Santana, da Costa, Alexandre André BA, Radice, Paolo, Peterlongo, Paolo, Papi, Laura, Engel, Christoph, Hahnen, Eric, Schmutzler, Rita K, Wappenschmidt, Barbara, Easton, Douglas F, Tischkowitz, Marc, Singer, Christian F, Tan, Yen Yen, Whittemore, Alice S, Sieh, Weiva, Brenton, James D, Yannoukakos, Drakoulis, Fostira, Florentia, Konstantopoulou, Irene, Soukupova, Jana, Vocka, Michal, Chenevix-Trench, Georgia, Pharoah, Paul DP, Antoniou, Antonis C, Goldgar, David E, Spurdle, Amanda B, and Michailidou, Kyriaki
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Cancer ,Breast Cancer ,Genetics ,Ovarian Cancer ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Humans ,Female ,Virulence ,BRCA1 Protein ,BRCA2 Protein ,Ovarian Neoplasms ,Genetic Predisposition to Disease ,Breast Neoplasms ,HEBON Investigators ,GEMO Study Collaborators ,AOCS Group ,CZECANCA Consortium ,Consortium of Investigators of Modifiers of BRCA1/2 ,Evidence-based Network for the Interpretation of Germline Mutant Alleles Consortium ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundThe distribution of ovarian tumour characteristics differs between germline BRCA1 and BRCA2 pathogenic variant carriers and non-carriers. In this study, we assessed the utility of ovarian tumour characteristics as predictors of BRCA1 and BRCA2 variant pathogenicity, for application using the American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) variant classification system.MethodsData for 10,373 ovarian cancer cases, including carriers and non-carriers of BRCA1 or BRCA2 pathogenic variants, were collected from unpublished international cohorts and consortia and published studies. Likelihood ratios (LR) were calculated for the association of ovarian cancer histology and other characteristics, with BRCA1 and BRCA2 variant pathogenicity. Estimates were aligned to ACMG/AMP code strengths (supporting, moderate, strong).ResultsNo histological subtype provided informative ACMG/AMP evidence in favour of BRCA1 and BRCA2 variant pathogenicity. Evidence against variant pathogenicity was estimated for the mucinous and clear cell histologies (supporting) and borderline cases (moderate). Refined associations are provided according to tumour grade, invasion and age at diagnosis.ConclusionsWe provide detailed estimates for predicting BRCA1 and BRCA2 variant pathogenicity based on ovarian tumour characteristics. This evidence can be combined with other variant information under the ACMG/AMP classification system, to improve classification and carrier clinical management.
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- 2023
45. Machine learning opens a doorway for microrheology with optical tweezers in living systems
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Smith, Matthew G., Radford, Jack, Febrianto, Eky, Ramírez, Jorge, O'Mahony, Helen, Matheson, Andrew B., Gibson, Graham M., Faccio, Daniele, and Tassieri, Manlio
- Subjects
Physics - Fluid Dynamics - Abstract
It has been argued [Tassieri, \textit{Soft Matter}, 2015, \textbf{11}, 5792] that linear microrheology with optical tweezers (MOT) of living systems ``\textit{is not an option}'', because of the wide gap between the observation time required to collect statistically valid data and the mutational times of the organisms under study. Here, we have taken a first step towards a possible solution of this problem by exploiting modern machine learning (ML) methods to reduce the duration of MOT measurements from several tens of minutes down to one second. This has been achieved by focusing on the analysis of computer simulated trajectories of an optically trapped particle suspended in a set of Newtonian fluids having viscosity values spanning three orders of magnitude, i.e. from $10^{-3}$ to $1$ Pa$\cdot$s. When the particle trajectory is analysed by means of conventional statistical mechanics principles, we explicate for the first time in literature the relationship between the required duration of MOT experiments ($T_m$) and the fluids relative viscosity ($\eta_r$) to achieve an uncertainty as low as $1\%$; i.e., $T_m\cong 17\eta_r^3$ minutes. This has led to further evidences explaining why conventional MOT measurements commonly underestimate the materials' viscoelastic properties, especially in the case of high viscous fluids or soft-solids such as gels and cells. Finally, we have developed a ML algorithm to determine the viscosity of Newtonian fluids that uses feature extraction on raw trajectories acquired at a kHz and for a duration of only one second, yet capable of returning viscosity values carrying an error as low as $\sim0.3\%$ at best; hence the opening of a doorway for MOT in living systems.
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- 2022
46. Diabetes mellitus increases risk of adverse drug reactions and death in hospitalised older people: the SENATOR trial
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Chinmayee, Anagha, Subbarayan, Selvarani, Myint, Phyo Kyaw, Cherubini, Antonio, Cruz-Jentoft, Alfonso J., Petrovic, Mirko, Gudmundsson, Adalsteinn, Byrne, Stephen, O’Mahony, Denis, and Soiza, Roy L.
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- 2024
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47. Intradermal Vaccination with PLGA Nanoparticles via Dissolving Microneedles and Classical Injection Needles
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Lee, Jihui, Neustrup, Malene A., Slütter, Bram, O’Mahony, Conor, Bouwstra, Joke A., and van der Maaden, Koen
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- 2024
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48. The feasibility and usability of mixed reality teaching in a hospital setting based on self-reported perceptions of medical students
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Michael Johnston, Megan O’Mahony, Niall O’Brien, Murray Connolly, Gabriella Iohom, Mohsin Kamal, Ahmed Shehata, and George Shorten
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Mixed reality ,Augmented reality ,Usability ,Feasibility ,Teaching ,Undergraduate ,Special aspects of education ,LC8-6691 ,Medicine - Abstract
Abstract Background Clinical teaching during encounters with real patients lies at the heart of medical education. Mixed reality (MR) using a Microsoft HoloLens 2 (HL2) offers the potential to address several challenges: including enabling remote learning; decreasing infection control risks; facilitating greater access to medical specialties; and enhancing learning by vertical integration of basic principles to clinical application. We aimed to assess the feasibility and usability of MR using the HL2 for teaching in a busy, tertiary referral university hospital. Methods This prospective observational study examined the use of the HL2 to facilitate a live two-way broadcast of a clinician-patient encounter, to remotely situated third and fourth year medical students. System Usability Scale (SUS) Scores were elicited from participating medical students, clinician, and technician. Feedback was also elicited from participating patients. A modified Evaluation of Technology-Enhanced Learning Materials: Learner Perceptions Questionnaire (mETELM) was completed by medical students and patients. Results This was a mixed methods prospective, observational study, undertaken in the Day of Surgery Assessment Unit. Forty-seven medical students participated. The mean SUS score for medical students was 71.4 (SD 15.4), clinician (SUS = 75) and technician (SUS = 70) indicating good usability. The mETELM Questionnaire using a 7-point Likert Scale demonstrated MR was perceived to be more beneficial than a PowerPoint presentation (Median = 7, Range 6–7). Opinion amongst the student cohort was divided as to whether the MR tutorial was as beneficial for learning as a live patient encounter would have been (Median = 5, Range 3–6). Students were positive about the prospect of incorporating of MR in future tutorials (Median = 7, Range 5–7). The patients’ mETELM results indicate the HL2 did not affect communication with the clinician (Median = 7, Range 7–7). The MR tutorial was preferred to a format based on small group teaching at the bedside (Median = 6, Range 4–7). Conclusions Our study findings indicate that MR teaching using the HL2 demonstrates good usability characteristics for providing education to medical students at least in a clinical setting and under conditions similar to those of our study. Also, it is feasible to deliver to remotely located students, although certain practical constraints apply including Wi-Fi and audio quality.
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- 2024
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49. The impact of the microbiota–gut–brain axis on endometriosis-associated symptoms: mechanisms and opportunities for personalised management strategies
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Francesca Hearn-Yeates, Andrew W Horne, Siobhain M O’Mahony, and Philippa T K Saunders
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antibiotics ,bloating ,diet ,dysbiosis ,endometriosis ,gut metabolome ,gut microbiome ,ibs ,inflammation ,microbiota–gut–brain axis ,mood disorders ,pain ,probiotics ,self-management strategies ,Reproduction ,QH471-489 ,Gynecology and obstetrics ,RG1-991 - Abstract
Endometriosis is a chronic inflammatory condition affecting one in ten women and those assigned female at birth, defined by the presence of endometrial-like tissue outside the uterus. It is commonly associated with pain, infertility, and mood disorders, and is often comorbid with other chronic pain conditions, such as irritable bowel syndrome. Recent research has identified a key role for the microbiota–gut–brain axis in health and a range of inflammatory and neurological disorders, prompting an exploration of its potential mechanistic role in endometriosis. Increased awareness of the impact of the gut microbiota within the patient community, combined with the often-detrimental side effects of current therapies, has motivated many to utilise self-management strategies, such as dietary modification and supplements, despite a lack of robust clinical evidence. Current research has characterised the gut microbiota in endometriosis patients and animal models. However, small cohorts and differing methodology have resulted in little consensus on the data. In this narrative review, we summarise research studies that have investigated the role of gut microbiota and their metabolic products in the development and progression of endometriosis lesions, before summarising insights from research into co-morbid conditions and discussing the reported impact of self-management strategies on symptoms of endometriosis. Finally, we suggest ways in which this promising field of research could be expanded to explore the role of specific bacteria, improve access to ‘microbial’ phenotyping, and develop personalised patient advice for reduction of symptoms such as chronic pain and bloating.
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- 2024
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50. The gut microbiota in persistent post-operative pain following breast cancer surgery
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Khaled Masaud, James M. Collins, Raul Cabrera Rubio, Mark Corrigan, Paul D. Cotter, Niall O’Brien, Ronan Bluett, Clare Keaveney Jimenez, Siobhain M. O’Mahony, and George D. Shorten
- Subjects
Medicine ,Science - Abstract
Abstract Persistent post-surgical pain (PPSP) is defined as pain which continues after a surgical operation in a significant form for at least three months (and is not related to pre-existing painful conditions). PPSP is a common, under-recognised, and important clinical problem which affects millions of patients worldwide. Preventative measures which are currently available include the selection of a minimally invasive surgical technique and an aggressive multimodal perioperative analgesic regimen. More recently, a role for the gut microbiota in pain modulation has become increasingly apparent. This study aims to investigate any relationship between the gut microbiota and PPSP. A prospective observational study of 68 female adult patients undergoing surgery for management of breast cancer was carried out. Stool samples from 45 of these patients were obtained to analyse the composition of the gut microbiota. Measures of pain and state-trait anxiety were also taken to investigate further dimensions in any relationship between the gut microbiota and PPSP. At 12 weeks postoperatively, 21 patients (51.2%) did not have any pain and 20 patients (48.8%) reported feeling pain that persisted at that time. Analysis of the gut microbiota revealed significantly lower alpha diversity (using three measures) in those patients reporting severe pain at the 60 min post-operative and the 12 weeks post-operative timepoints. A cluster of taxa represented by Bifidobacterium longum, and Faecalibacterium prausnitzii was closely associated with those individuals reporting no pain at 12 weeks postoperatively, while Megamonas hypermegale, Bacteroides pectinophilus, Ruminococcus bromii, and Roseburia hominis clustered relatively closely in the group of patients fulfilling the criteria for persistent post-operative pain. We report for the first time specific associations between the gut microbiota composition and the presence or absence of PPSP. This may provide further insights into mechanisms behind the role of the gut microbiota in the development of PPSP and could inform future treatment strategies.
- Published
- 2024
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