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46,501 results on '"Easton A"'

1. Digit Recognition using Multimodal Spiking Neural Networks

Author

Bjorndahl, William, Easton, Jack, Modoff, Austin, Larson, Eric C., Camp, Joseph, and Rangarajan, Prasanna

Subjects
Electrical Engineering and Systems Science - Audio and Speech Processing, Computer Science - Computer Vision and Pattern Recognition, Computer Science - Multimedia, Computer Science - Sound
Abstract

Spiking neural networks (SNNs) are the third generation of neural networks that are biologically inspired to process data in a fashion that emulates the exchange of signals in the brain. Within the Computer Vision community SNNs have garnered significant attention due in large part to the availability of event-based sensors that produce a spatially resolved spike train in response to changes in scene radiance. SNNs are used to process event-based data due to their neuromorphic nature. The proposed work examines the neuromorphic advantage of fusing multiple sensory inputs in classification tasks. Specifically we study the performance of a SNN in digit classification by passing in a visual modality branch (Neuromorphic-MNIST [N-MNIST]) and an auditory modality branch (Spiking Heidelberg Digits [SHD]) from datasets that were created using event-based sensors to generate a series of time-dependent events. It is observed that multi-modal SNNs outperform unimodal visual and unimodal auditory SNNs. Furthermore, it is observed that the process of sensory fusion is insensitive to the depth at which the visual and auditory branches are combined. This work achieves a 98.43% accuracy on the combined N-MNIST and SHD dataset using a multimodal SNN that concatenates the visual and auditory branches at a late depth., Comment: 4 pages, 2 figures, submitted to 2025 IEEE International Conference on Acoustics, Speech, and Signal Processing

Published
2024

2. Trust, Because You Can't Verify:Privacy and Security Hurdles in Education Technology Acquisition Practices

Author

Kelso, Easton, Soneji, Ananta, Rahaman, Sazzadur, Soshitaishvili, Yan, and Hasan, Rakibul

Subjects
Computer Science - Computers and Society
Abstract

The education technology (EdTech) landscape is expanding rapidly in higher education institutes (HEIs). This growth brings enormous complexity. Protecting the extensive data collected by these tools is crucial for HEIs as data breaches and misuses can have dire security and privacy consequences on the data subjects, particularly students, who are often compelled to use these tools. This urges an in-depth understanding of HEI and EdTech vendor dynamics, which is largely understudied. To address this gap, we conducted a semi-structured interview study with 13 participants who are in EdTech leadership roles at seven HEIs. Our study uncovers the EdTech acquisition process in the HEI context, the consideration of security and privacy issues throughout that process, the pain points of HEI personnel in establishing adequate protection mechanisms in service contracts, and their struggle in holding vendors accountable due to a lack of visibility into their system and power-asymmetry, among other reasons. We discuss certain observations about the status quo and conclude with recommendations for HEIs, researchers, and regulatory bodies to improve the situation.

Published
2024

3. Data integration methods for micro-randomized trials

Author

Huch, Easton, Nahum-Shani, Inbal, Potter, Lindsey, Lam, Cho, Wetter, David W., and Dempsey, Walter

Subjects
Statistics - Methodology
Abstract

Existing statistical methods for the analysis of micro-randomized trials (MRTs) are designed to estimate causal excursion effects using data from a single MRT. In practice, however, researchers can often find previous MRTs that employ similar interventions. In this paper, we develop data integration methods that capitalize on this additional information, leading to statistical efficiency gains. To further increase efficiency, we demonstrate how to combine these approaches according to a generalization of multivariate precision weighting that allows for correlation between estimates, and we show that the resulting meta-estimator possesses an asymptotic optimality property. We illustrate our methods in simulation and in a case study involving two MRTs in the area of smoking cessation.

Published
2024

4. eKichabi v2: Designing and Scaling a Dual-Platform Agricultural Technology in Rural Tanzania

Author

Raghunath, Ananditha, Metzger, Alexander, Easton, Hans, Liu, XunMei, Wang, Fanchong, Wang, Yunqi, Zhao, Yunwei, Mpogole, Hosea, and Anderson, Richard

Subjects
Computer Science - Human-Computer Interaction
Abstract

Although farmers in Sub-Saharan Africa are accessing feature phones and smartphones at historically high rates, they face challenges finding a robust network of agricultural contacts. With collaborators, we conduct a quantitative survey of 1014 agricultural households in Kagera, Tanzania to characterize technology access, use, and comfort levels in the region. Recognizing the paucity of research on dual-platform technologies that cater to both feature phone and smartphone users, we develop and deploy eKichabi v2, a searchable directory of 9833 agriculture-related enterprises accessible via a USSD application and an Android application. To bridge the gap in affordances between the two applications, we conduct a mixed methods pilot leveraging mobile money agents as intermediators for our USSD application's users. Through our investigations, we identify the advantages, obstacles, and critical considerations in the design, implementation, and scalability of agricultural information systems tailored to both feature phone and smartphone users in Sub-Saharan Africa.

Published
2024
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5. Lasting Differences: Math Grades and Gender. Research Report

Author

University of Chicago Consortium on School Research, John Q. Easton, and Briana Diaz

Abstract

Research studies show that students' grades are more predictive than test scores of their future academic success, including high school and post-secondary outcomes. Chicago Public Schools (CPS) recognizes the importance of grades through its longstanding "Bs or Better" campaign. Yet within CPS, boys' grades are consistently lower than girls' grades. CPS leaders and educators want to meet their goal of Bs or better and strong educational outcomes for all students, and they are in conversation about how they're supporting boys. This study aims to provide insights into this difference in boys' and girls' grades in Chicago by looking first at one grade level and one subject area--ninth-grade math (algebra and geometry)--using two school years of data, 2016-17 and 2017-18. The findings are specific to math students in these years, and also suggest what may (and may not) be driving differences in other grades and subjects. [Additional funding for this report was provided by the Hyman Milgrom Opportunity Fund at the University of Chicago and the Consortium Investors Council.]

Published
2023

11. Investing in Adolescents: High School Climate and Organizational Context Shape Student Development and Educational Attainment. Research Summary

Author

University of Chicago Consortium on School Research, Shanette C. Porter, C. Kirabo Jackson, Sebastián Kiguel, and John Q. Easton

Abstract

Evidence in psychology and economics has converged on an understanding of what matters for students' learning and what influences their life trajectories. While earlier work focused on the role of large scale assessment test scores, more recent research emphasizes the importance of socioemotional skills, experiences, and mindsets--such as conflict resolution, conscientiousness, goal-setting, study skills, belonging, and adaptive self-beliefs--for thriving in adolescence and into adulthood. This updated scientific knowledge about socioemotional factors has mobilized action in educational policy. This report examines on what schools can do well to positively affect students' long-term trajectories. The findings show the value of taking a holistic view of adolescents, and that fostering students' engagement and a challenging, supportive environment for them are the most important things schools can do. The findings and interpretive summary offer insights on some of the most-discussed K-12 policies and practices today, including test scores, school quality metrics, school climate, and student voice.

Published
2023

12. The impact of living with assistance dog placements on quality of life in children and adults with autism spectrum disorder or a physical disability: A longitudinal service evaluation

Author

Shoesmith, Emily, Gibsone, Selina, Bracher, Ed, Smolkovič, Iris, Jennings, Kelly, Viles, Laura, Easton, Kate, and Ratschen, Elena

Subjects
assistance dogs, autism, autism spectrum disorder, physical disability, service evaluation
Abstract

Assistance dogs are highly trained animals to support individuals with disabilities and medical conditions. Evidence suggests the support provided by an assistance dog can extend beyond physical assistance to therapeutic and communicative domains. However, there is limited research exploring the lived experience of assistance dog placements in the United Kingdom (UK) over an extended period of time. This longitudinal service evaluation was designed to evaluate the placement of assistance dogs, trained by the charity Dogs for Good, with adults and children with autism or a physical disability in the UK. Goals and expectations of being matched with an assistance dog prior to placement, and perceptions of how these dogs have impacted the quality of life of adults and children with autism and/or a physical disability and their families were assessed. Service users who had applied for an assistance dog via the Dogs for Good charity (n = 307) were contacted and invited to complete questionnaires at five different time points (pre-dog placement, and 6-, 12-, 24-, and 36-months post dog-placement). Repeated-measures ANOVAs were conducted to determine if there were significant changes to quality of life over time. Mean quality of life scores improved significantly for all service users. Responses to free-text questions were thematically analysed, and three main themes were identified from the free-text responses: goals and expectations for assistance dog pre-placement (e.g., enhancing independence, physical functioning and wellbeing), the positive impact of the assistance dog post-placement (e.g., promoting independence, development of the human-animal bond, improving wider family dynamics, and reducing stigma), and satisfaction with the service. The findings complement and extend previous insights into the impact of assistance dogs on people with autism or a physical disability. They also highlight some challenges associated with the placement of assistance dogs and indicate the need to consider the development of further targeted support strategies.

Published
2024
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13. A Robust Mixed-Effects Bandit Algorithm for Assessing Mobile Health Interventions

Author

Huch, Easton K., Shi, Jieru, Abbott, Madeline R., Golbus, Jessica R., Moreno, Alexander, and Dempsey, Walter H.

Subjects
Statistics - Machine Learning, Computer Science - Machine Learning
Abstract

Mobile health leverages personalized, contextually-tailored interventions optimized through bandit and reinforcement learning algorithms. Despite its promise, challenges like participant heterogeneity, nonstationarity, and nonlinearity in rewards hinder algorithm performance. We propose a robust contextual bandit algorithm, termed "DML-TS-NNR", that simultaneously addresses these challenges via (1) modeling the differential reward with user- and time-specific incidental parameters, (2) network cohesion penalties, and (3) debiased machine learning for flexible estimation of baseline rewards. We establish a high-probability regret bound that depends solely on the dimension of the differential reward model. This feature enables us to achieve robust regret bounds even when the baseline reward is highly complex. We demonstrate the superior performance of the DML-TS-NNR algorithm in a simulation and two off-policy evaluation studies.

Published
2023

14. On the Path to Becoming a Chicago Public School Principal. Research Report

Author

NORC at the University of Chicago, University of Chicago Consortium on School Research, University of North Carolina at Chapel Hill, School of Education, Molly F. Gordon, Angel X. Bohannon, John Q. Easton, Alyssa Blanchard, Lauren Sartain, and Cole Smith

Abstract

The purpose of this qualitative study was to examine the backgrounds, experiences, and supports of Chicago Public School (CPS) principals as they prepared for the principalship and to identify where gaps exist so that policymakers and principal preparation programs can better support leadership development. Researchers interviewed 20 early career school principals in CPS between 2020 and 2021 to learn about their backgrounds and the roles they had prior to the principalship, their formal and informal preparation experiences, and the kinds of learning opportunities and skills they wished they had before assuming the role. Findings indicate that it takes a wide range of skills to be a successful principal, including both interpersonal or "people" skills as well as intrapersonal or "emotional intelligence" skills, along with specific organizational leadership and managerial skills. Principals did not learn essential skills in one place or in one setting, but through a variety of on-the-job learning experiences -- in both education and non-education related positions. Principals who previously served as an assistant principal indicated that the role best prepared them to lead their own school. Some indicated feeling underprepared in certain aspects of the job and called for more pre-service supports and mentoring in areas such as school budgeting and navigating central office systems. Districts and principal preparation programs must consider that strong school leadership requires a wide range of skills, making it unlikely that a single program or professional development opportunity can teach all the skills and behaviors good principals need to succeed. A "one-size-fits all" approach to training principals may be insufficient, suggesting a more tailored approach to supporting prospective school leader development would be most beneficial.

Published
2023

15. Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Author

Kentistou, Katherine A., Kaisinger, Lena R., Stankovic, Stasa, Vaudel, Marc, Mendes de Oliveira, Edson, Messina, Andrea, Walters, Robin G., Liu, Xiaoxi, Busch, Alexander S., Helgason, Hannes, Thompson, Deborah J., Santoni, Federico, Petricek, Konstantin M., Zouaghi, Yassine, Huang-Doran, Isabel, Gudbjartsson, Daniel F., Bratland, Eirik, Lin, Kuang, Gardner, Eugene J., Zhao, Yajie, Jia, Raina Y., Terao, Chikashi, Riggan, Marjorie J., Bolla, Manjeet K., Yazdanpanah, Mojgan, Yazdanpanah, Nahid, Bradfield, Jonathan P., Broer, Linda, Campbell, Archie, Chasman, Daniel I., Cousminer, Diana L., Franceschini, Nora, Franke, Lude H., Girotto, Giorgia, He, Chunyan, Järvelin, Marjo-Riitta, Joshi, Peter K., Kamatani, Yoichiro, Karlsson, Robert, Luan, Jian’an, Lunetta, Kathryn L., Mägi, Reedik, Mangino, Massimo, Medland, Sarah E., Meisinger, Christa, Noordam, Raymond, Nutile, Teresa, Concas, Maria Pina, Polašek, Ozren, Porcu, Eleonora, Ring, Susan M., Sala, Cinzia, Smith, Albert V., Tanaka, Toshiko, van der Most, Peter J., Vitart, Veronique, Wang, Carol A., Willemsen, Gonneke, Zygmunt, Marek, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Auer, Paul L., Barnes, Catriona L. K., Beckmann, Matthias W., Berrington de Gonzalez, Amy, Bogdanova, Natalia V., Bojesen, Stig E., Brenner, Hermann, Buring, Julie E., Canzian, Federico, Chang-Claude, Jenny, Couch, Fergus J., Cox, Angela, Crisponi, Laura, Czene, Kamila, Daly, Mary B., Demerath, Ellen W., Dennis, Joe, Devilee, Peter, De Vivo, Immaculata, Dörk, Thilo, Dunning, Alison M., Dwek, Miriam, Eriksson, Johan G., Fasching, Peter A., Fernandez-Rhodes, Lindsay, Ferreli, Liana, Fletcher, Olivia, Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A., González-Neira, Anna, Grallert, Harald, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Hakonarson, Hakon, Hart, Roger J., Hickey, Martha, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Hottenga, Jouke-Jan, Hu, Frank B., Huebner, Hanna, Hunter, David J., Jernström, Helena, John, Esther M., Karasik, David, Khusnutdinova, Elza K., Kristensen, Vessela N., Lacey, James V., Lambrechts, Diether, Launer, Lenore J., Lind, Penelope A., Lindblom, Annika, Magnusson, Patrik K. E., Mannermaa, Arto, McCarthy, Mark I., Meitinger, Thomas, Menni, Cristina, Michailidou, Kyriaki, Millwood, Iona Y., Milne, Roger L., Montgomery, Grant W., Nevanlinna, Heli, Nolte, Ilja M., Nyholt, Dale R., Obi, Nadia, O’Brien, Katie M., Offit, Kenneth, Oldehinkel, Albertine J., Ostrowski, Sisse R., Palotie, Aarno, Pedersen, Ole B., Peters, Annette, Pianigiani, Giulia, Plaseska-Karanfilska, Dijana, Pouta, Anneli, Pozarickij, Alfred, Radice, Paolo, Rennert, Gad, Rosendaal, Frits R., Ruggiero, Daniela, Saloustros, Emmanouil, Sandler, Dale P., Schipf, Sabine, Schmidt, Carsten O., Schmidt, Marjanka K., Small, Kerrin, Spedicati, Beatrice, Stampfer, Meir, Stone, Jennifer, Tamimi, Rulla M., Teras, Lauren R., Tikkanen, Emmi, Turman, Constance, Vachon, Celine M., Wang, Qin, Winqvist, Robert, Wolk, Alicja, Zemel, Babette S., Zheng, Wei, van Dijk, Ko W., Alizadeh, Behrooz Z., Bandinelli, Stefania, Boerwinkle, Eric, Boomsma, Dorret I., Ciullo, Marina, Chenevix-Trench, Georgia, Cucca, Francesco, Esko, Tõnu, Gieger, Christian, Grant, Struan F. A., Gudnason, Vilmundur, Hayward, Caroline, Kolčić, Ivana, Kraft, Peter, Lawlor, Deborah A., Martin, Nicholas G., Nøhr, Ellen A., Pedersen, Nancy L., Pennell, Craig E., Ridker, Paul M., Robino, Antonietta, Snieder, Harold, Sovio, Ulla, Spector, Tim D., Stöckl, Doris, Sudlow, Cathie, Timpson, Nic J., Toniolo, Daniela, Uitterlinden, André, Ulivi, Sheila, Völzke, Henry, Wareham, Nicholas J., Widen, Elisabeth, Wilson, James F., Pharoah, Paul D. P., Li, Liming, Easton, Douglas F., Njølstad, Pål R., Sulem, Patrick, Murabito, Joanne M., Murray, Anna, Manousaki, Despoina, Juul, Anders, Erikstrup, Christian, Stefansson, Kari, Horikoshi, Momoko, Chen, Zhengming, Farooqi, I. Sadaf, Pitteloud, Nelly, Johansson, Stefan, Day, Felix R., Perry, John R. B., and Ong, Ken K.

Published
2024
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16. Disentangling the relationships of body mass index and circulating sex hormone concentrations in mammographic density using Mendelian randomization

Author

Haas, Cameron B., Chen, Hongjie, Harrison, Tabitha, Fan, Shaoqi, Gago-Dominguez, Manuela, Castelao, Jose E., Bolla, Manjeet K., Wang, Qin, Dennis, Joe, Michailidou, Kyriaki, Dunning, Alison M., Easton, Douglas F., Antoniou, Antonis C., Hall, Per, Czene, Kamila, Andrulis, Irene L., Mulligan, Anna Marie, Milne, Roger L., Fasching, Peter A., Haeberle, Lothar, Garcia-Closas, Montserrat, Ahearn, Thomas, Gierach, Gretchen L., Haiman, Christopher, Maskarinec, Gertraud, Couch, Fergus J., Olson, Janet E., John, Esther M., Chenevix-Trench, Geogia, Berrington de Gonzalez, Amy, Jones, Michael, Stone, Jennifer, Murphy, Rachel, Aronson, Kristan J., Wernli, Karen J., Hsu, Li, Vachon, Celine, Tamimi, Rulla M., and Lindström, Sara

Published
2024
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20. Isolating Neighborhood Trajectory Computations in Non-Autonomous Systems Including the Elliptic Restricted Three-Body Problem

Author

Anderson, Rodney L., Easton, Robert W., and Lo, Martin W.

Subjects
Mathematics - Dynamical Systems
Abstract

Isolating block and isolating neighborhood methods have previously been implemented to find transit trajectories and orbits around libration points in the autonomous circular restricted three-body problem. For some applications, the direct computation of these types of trajectories in non-autonomous models more closely approximating real-world ephemerides is beneficial. Here, we apply isolating neighborhood methods to non-autonomous systems, including the elliptic restricted three-body problem (ERTBP). Specifically, simplified isolating neighborhood boundaries are computed around libration points in the ERTBP. These boundaries are used in combination with a bisection method to compute the forward asymptotic trajectories of the isolated invariant set and track orbits around a libration point.

Published
2023

21. Evaluating Field-Effect Separation on Rare Earth and Critical Metals

Author

Benjamin Schroeder, Michael Free, Prashant Sarswat, Easton Sadler, Jacob Burke, and Zoe Evans

Subjects
rare earths, separation, magnetic field, electric field, microfluidics, Electrical engineering. Electronics. Nuclear engineering, TK1-9971
Abstract

The unique electromagnetic properties of rare earth elements (REEs) have led to rapid technological advances, creating a sharp increase in demand for these materials. The inherent challenges of separating REEs and the significant drawbacks of existing processes have driven the development of a new method known as field-effect separation (FES). This technology leverages electrical and magnetic fields to achieve separation by exploiting the differences in magnetic moments or effective charges of REEs in solution. Experiments on REEs were conducted using a microchannel based separation device, which confines fluid flow to facilitate separation within a field, with metal cations in solution being transported based on their respective electrostatic or magnetic properties. The results demonstrate that separation based on effective charge or paramagnetic properties is achievable. The confinement of fluid flow to microchannels allowed advective and osmotic forces to be suppressed sufficiently such that a reasonable separation of ions was achieved, though the impact of these forces were not completely removed. This innovative approach promises to improve the efficiency and effectiveness of REE separation, addressing both the growing demand and the limitations of current methods.

Published
2024
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22. Assessment of long-term psychosocial outcomes in N-methyl-D-aspartate receptor encephalitis – the SAPIENCE study protocol

Author

Ole Jonas Boeken, Josephine Heine, Marta Duda-Sikula, Víctor Patricio, Géraldine Picard, Chloé Buttard, Marie Benaiteau, Álvaro Mendes, Fuchsia Howard, Ava Easton, Donata Kurpas, Jérôme Honnorat, Josep Dalmau, and Carsten Finke

Subjects
NMDA receptor encephalitis, Health-related quality of life, Patient-reported outcome measures, Patient-reported experience measures, Cognitive outcomes, Post-acute interventions, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background N-methyl-D-aspartate-receptor (NMDAR) encephalitis is a rare neurological autoimmune disease with severe neuropsychiatric symptoms during the acute phase. Despite good functional neurological recovery, most patients continue to experience cognitive, psychiatric, psychological, and social impairments years after the acute phase. However, the precise nature and evolving patterns over time of these long-term consequences remain unclear, and their implications for the well-being and quality of life of predominantly young patients have yet to be thoroughly examined. Methods SAPIENCE is a European multi-center (n = 3) prospective observational cohort study studying the long-term cognitive, psychiatric, psychological, and social outcome in patients with NMDAR encephalitis. The study consists of three interconnected levels. Level 1 comprises a qualitative interview and focus groups with patients and their caregivers. Level 2 consists of a condensed form of the interview, standardized questionnaires, and a detailed neuropsychological examination of patients. Level 3 involves an online survey that will be open to patients world-wide and explores patient-reported outcomes (PROMs), and patient-reported experiences (PREMs) in association with clinical and cognitive outcomes. Levels 1 to 3 will progressively contribute developing of structured interviews, survey questions, and treatment guidelines by informing one another. Discussion SAPIENCE is an in-depth study of the long-term effects of NMDAR encephalitis and bridges the gap between standardized assessments and individual patient experiences, intending to improve patient care and to increase awareness of the psychosocial long-term consequences of the disease. Through collaboration of experts in clinical neurology and social and health psychology across Europe, SAPIENCE aims to create online assessment tools and formulate guidelines for patient-centered post-acute care that will help enhance the quality of life for patients and caregivers.

Published
2024
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24. Reaching for Improvement: Teacher Evaluation and Its Role in Instructional Improvement. Research Summary

Author

University of Chicago Consortium on School Research, Shyjka, Andria, and Easton, John Q.

Abstract

This research summary provides the key findings and interpretive summary--chapters 3 and 4--from the full report, "Reaching for Improvement: Teacher Evaluation and its Role in Instructional Improvement." The full report contains additional details on the context, methodology, and findings of this study. This document has minor differences to ensure clarity in its shorter form. This study examined teachers' experiences with instructional improvement in seven Chicago Public Schools from 2017-18 to ask: What organizational conditions and capacities supported evaluation-driven instructional improvement? [For the full Research Report, see ED623750.]

Published
2022

25. Publisher Correction: Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Author

Kentistou, Katherine A., Kaisinger, Lena R., Stankovic, Stasa, Vaudel, Marc, Mendes de Oliveira, Edson, Messina, Andrea, Walters, Robin G., Liu, Xiaoxi, Busch, Alexander S., Helgason, Hannes, Thompson, Deborah J., Santoni, Federico, Petricek, Konstantin M., Zouaghi, Yassine, Huang-Doran, Isabel, Gudbjartsson, Daniel F., Bratland, Eirik, Lin, Kuang, Gardner, Eugene J., Zhao, Yajie, Jia, Raina Y., Terao, Chikashi, Riggan, Marjorie J., Bolla, Manjeet K., Yazdanpanah, Mojgan, Yazdanpanah, Nahid, Bradfield, Jonathan P., Broer, Linda, Campbell, Archie, Chasman, Daniel I., Cousminer, Diana L., Franceschini, Nora, Franke, Lude H., Girotto, Giorgia, He, Chunyan, Järvelin, Marjo-Riitta, Joshi, Peter K., Kamatani, Yoichiro, Karlsson, Robert, Luan, Jian’an, Lunetta, Kathryn L., Mägi, Reedik, Mangino, Massimo, Medland, Sarah E., Meisinger, Christa, Noordam, Raymond, Nutile, Teresa, Concas, Maria Pina, Polašek, Ozren, Porcu, Eleonora, Ring, Susan M., Sala, Cinzia, Smith, Albert V., Tanaka, Toshiko, van der Most, Peter J., Vitart, Veronique, Wang, Carol A., Willemsen, Gonneke, Zygmunt, Marek, Ahearn, Thomas U., Andrulis, Irene L., Anton-Culver, Hoda, Antoniou, Antonis C., Auer, Paul L., Barnes, Catriona L. K., Beckmann, Matthias W., Berrington de Gonzalez, Amy, Bogdanova, Natalia V., Bojesen, Stig E., Brenner, Hermann, Buring, Julie E., Canzian, Federico, Chang-Claude, Jenny, Couch, Fergus J., Cox, Angela, Crisponi, Laura, Czene, Kamila, Daly, Mary B., Demerath, Ellen W., Dennis, Joe, Devilee, Peter, De Vivo, Immaculata, Dörk, Thilo, Dunning, Alison M., Dwek, Miriam, Eriksson, Johan G., Fasching, Peter A., Fernandez-Rhodes, Lindsay, Ferreli, Liana, Fletcher, Olivia, Gago-Dominguez, Manuela, García-Closas, Montserrat, García-Sáenz, José A., González-Neira, Anna, Grallert, Harald, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Hakonarson, Hakon, Hart, Roger J., Hickey, Martha, Hooning, Maartje J., Hoppe, Reiner, Hopper, John L., Hottenga, Jouke-Jan, Hu, Frank B., Huebner, Hanna, Hunter, David J., Jernström, Helena, John, Esther M., Karasik, David, Khusnutdinova, Elza K., Kristensen, Vessela N., Lacey, James V., Lambrechts, Diether, Launer, Lenore J., Lind, Penelope A., Lindblom, Annika, Magnusson, Patrik K. E., Mannermaa, Arto, McCarthy, Mark I., Meitinger, Thomas, Menni, Cristina, Michailidou, Kyriaki, Millwood, Iona Y., Milne, Roger L., Montgomery, Grant W., Nevanlinna, Heli, Nolte, Ilja M., Nyholt, Dale R., Obi, Nadia, O’Brien, Katie M., Offit, Kenneth, Oldehinkel, Albertine J., Ostrowski, Sisse R., Palotie, Aarno, Pedersen, Ole B., Peters, Annette, Pianigiani, Giulia, Plaseska-Karanfilska, Dijana, Pouta, Anneli, Pozarickij, Alfred, Radice, Paolo, Rennert, Gad, Rosendaal, Frits R., Ruggiero, Daniela, Saloustros, Emmanouil, Sandler, Dale P., Schipf, Sabine, Schmidt, Carsten O., Schmidt, Marjanka K., Small, Kerrin, Spedicati, Beatrice, Stampfer, Meir, Stone, Jennifer, Tamimi, Rulla M., Teras, Lauren R., Tikkanen, Emmi, Turman, Constance, Vachon, Celine M., Wang, Qin, Winqvist, Robert, Wolk, Alicja, Zemel, Babette S., Zheng, Wei, van Dijk, Ko W., Alizadeh, Behrooz Z., Bandinelli, Stefania, Boerwinkle, Eric, Boomsma, Dorret I., Ciullo, Marina, Chenevix-Trench, Georgia, Cucca, Francesco, Esko, Tõnu, Gieger, Christian, Grant, Struan F. A., Gudnason, Vilmundur, Hayward, Caroline, Kolčić, Ivana, Kraft, Peter, Lawlor, Deborah A., Martin, Nicholas G., Nøhr, Ellen A., Pedersen, Nancy L., Pennell, Craig E., Ridker, Paul M., Robino, Antonietta, Snieder, Harold, Sovio, Ulla, Spector, Tim D., Stöckl, Doris, Sudlow, Cathie, Timpson, Nic J., Toniolo, Daniela, Uitterlinden, André, Ulivi, Sheila, Völzke, Henry, Wareham, Nicholas J., Widen, Elisabeth, Wilson, James F., Pharoah, Paul D. P., Li, Liming, Easton, Douglas F., Njølstad, Pål R., Sulem, Patrick, Murabito, Joanne M., Murray, Anna, Manousaki, Despoina, Juul, Anders, Erikstrup, Christian, Stefansson, Kari, Horikoshi, Momoko, Chen, Zhengming, Farooqi, I. Sadaf, Pitteloud, Nelly, Johansson, Stefan, Day, Felix R., Perry, John R. B., and Ong, Ken K.

Published
2024
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26. Integrome signatures of lentiviral gene therapy for SCID-X1 patients.

Author

Yan, Koon-Kiu, Condori, Jose, Ma, Zhijun, Metais, Jean-Yves, Ju, Bensheng, Ding, Liang, Dhungana, Yogesh, Palmer, Lance, Langfitt, Deanna, Ferrara, Francesca, Throm, Robert, Shi, Hao, Risch, Isabel, Bhatara, Sheetal, Shaner, Bridget, Lockey, Timothy, Talleur, Aimee, Easton, John, Meagher, Michael, Puck, Jennifer, Zhou, Sheng, Mamcarz, Ewelina, Gottschalk, Stephen, Yu, Jiyang, and Cowan, Morton

Abstract

Lentiviral vector (LV)-based gene therapy holds promise for a broad range of diseases. Analyzing more than 280,000 vector integration sites (VISs) in 273 samples from 10 patients with X-linked severe combined immunodeficiency (SCID-X1), we discovered shared LV integrome signatures in 9 of 10 patients in relation to the genomics, epigenomics, and 3D structure of the human genome. VISs were enriched in the nuclear subcompartment A1 and integrated into super-enhancers close to nuclear pore complexes. These signatures were validated in T cells transduced with an LV encoding a CD19-specific chimeric antigen receptor. Intriguingly, the one patient whose VISs deviated from the identified integrome signatures had a distinct clinical course. Comparison of LV and gamma retrovirus integromes regarding their 3D genome signatures identified differences that might explain the lower risk of insertional mutagenesis in LV-based gene therapy. Our findings suggest that LV integrome signatures, shaped by common features such as genome organization, may affect the efficacy of LV-based cellular therapies.

Published
2023

27. Annual (2023) taxonomic update of RNA-directed RNA polymerase-encoding negative-sense RNA viruses (realm Riboviria: kingdom Orthornavirae: phylum Negarnaviricota).

Author

Bukreyev, Alexander, Burt, Felicity, Büttner, Carmen, Calisher, Charles, Cao, Mengji, Casas, Inmaculada, Chandran, Kartik, Charrel, Rémi, Kumar Chaturvedi, Krishna, Chooi, Kar, Crane, Anya, Dal Bó, Elena, Carlos de la Torre, Juan, de Souza, William, de Swart, Rik, Debat, Humberto, Dheilly, Nolwenn, Di Paola, Nicholas, Di Serio, Francesco, Dietzgen, Ralf, Digiaro, Michele, Drexler, J, Duprex, W, Dürrwald, Ralf, Easton, Andrew, Elbeaino, Toufic, Ergünay, Koray, Feng, Guozhong, Firth, Andrew, Fooks, Anthony, Formenty, Pierre, Freitas-Astúa, Juliana, Gago-Zachert, Selma, Laura García, María, García-Sastre, Adolfo, Garrison, Aura, Gaskin, Thomas, Gong, Wenjie, Gonzalez, Jean-Paul, de Bellocq, JoëlleGoüy, Griffiths, Anthony, Groschup, Martin, Günther, Ines, Günther, Stephan, Hammond, John, Hasegawa, Yusuke, Hayashi, Kazusa, Hepojoki, Jussi, Higgins, Colleen, Hongō, Seiji, Horie, Masayuki, Hughes, Holly, Hume, Adam, Hyndman, Timothy, Ikeda, Kenichi, Jiāng, Dàohóng, Jonson, Gilda, Junglen, Sandra, Klempa, Boris, Klingström, Jonas, Kondō, Hideki, Koonin, Eugene, Krupovic, Mart, Kubota, Kenji, Kurath, Gael, Laenen, Lies, Lambert, Amy, Lǐ, Jiànróng, Li, Jun-Min, Liu, Ran, Lukashevich, Igor, MacDiarmid, Robin, Maes, Piet, Marklewitz, Marco, Marshall, Sergio, Marzano, Shin-Yi, McCauley, John, Mirazimi, Ali, Mühlberger, Elke, Nabeshima, Tomoyuki, Naidu, Rayapati, Natsuaki, Tomohide, Navarro, Beatriz, Navarro, José, Neriya, Yutaro, Netesov, Sergey, Neumann, Gabriele, Nowotny, Norbert, Nunes, Márcio, Ochoa-Corona, Francisco, Okada, Tomoyuki, Palacios, Gustavo, Pallás, Vicente, Papa, Anna, Paraskevopoulou, Sofia, Parrish, Colin, Pauvolid-Corrêa, Alex, Pawęska, Janusz, Pérez, Daniel, and Pfaff, Florian

Subjects
Aliusviridae, Arenaviridae, Articulavirales, Artoviridae, Aspiviridae, Bornaviridae, Bunyavirales, Crepuscuviridae, Discoviridae, Filoviridae, Fimoviridae, Goujianvirales, Hantaviridae, ICTV, International Committee on Taxonomy of Viruses, Jingchuvirales, Lispiviridae, Mononegavirales, Muvirales, Mymonaviridae, Myriaviridae, Nairoviridae, Natareviridae, Negarnaviricota, Nyamiviridae, Orthomyxoviridae, Orthornavirae, Paramyxoviridae, Peribunyaviridae, Phasmaviridae, Phenuiviridae, Pneumoviridae, Rhabdoviridae, Riboviria, Serpentovirales, Sunviridae, Tenuivirus, Tosoviridae, Tospoviridae, Tulasviridae, articulaviral, bunyaviral, bunyavirus, goujianviral, megaclassification, megataxonomy, mononegaviral, muviral, negarnaviricot, serpentoviral, virus classification, virus nomenclature, virus taxonomy, Negative-Sense RNA Viruses, RNA Viruses, RNA-Dependent RNA Polymerase
Abstract

In April 2023, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by one new family, 14 new genera, and 140 new species. Two genera and 538 species were renamed. One species was moved, and four were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

Published
2023

28. Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer‐specific survival

Author

Morra, Anna, Schreurs, Maartje AC, Andrulis, Irene L, Anton‐Culver, Hoda, Augustinsson, Annelie, Beckmann, Matthias W, Behrens, Sabine, Bojesen, Stig E, Bolla, Manjeet K, Brauch, Hiltrud, Broeks, Annegien, Buys, Saundra S, Camp, Nicola J, Castelao, Jose E, Cessna, Melissa H, Chang‐Claude, Jenny, Chung, Wendy K, Sahlberg, Kristine K, Børresen‐Dale, Anne‐Lise, Gram, Inger Torhild, Olsen, Karina Standahl, Engebråten, Olav, Naume, Bjørn, Geisler, Jürgen, OSBREAC, Alnæs, Grethe I Grenaker, Colonna, Sarah V, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Dennis, Joe, Devilee, Peter, Dörk, Thilo, Dunning, Alison M, Dwek, Miriam, Easton, Douglas F, Eccles, Diana M, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Fehm, Tanja N, Figueroa, Jonine D, Flyger, Henrik, Gabrielson, Marike, Gago‐Dominguez, Manuela, García‐Closas, Montserrat, García‐Sáenz, José A, Genkinger, Jeanine, Grassmann, Felix, Gündert, Melanie, Hahnen, Eric, Haiman, Christopher A, Hamann, Ute, Harrington, Patricia A, Hartikainen, Jaana M, Hoppe, Reiner, Hopper, John L, Houlston, Richard S, Howell, Anthony, Clarke, Christine, Marsh, Deborah, Scott, Rodney, Baxter, Robert, Yip, Desmond, Carpenter, Jane, Davis, Alison, Pathmanathan, Nirmala, Simpson, Peter, Graham, J Dinny, Sachchithananthan, Mythily, Amor, David, Andrews, Lesley, Antill, Yoland, Balleine, Rosemary, Beesley, Jonathan, Bennett, Ian, Bogwitz, Michael, Botes, Leon, Brennan, Meagan, Brown, Melissa, Buckley, Michael, Burke, Jo, Butow, Phyllis, Caldon, Liz, Campbell, Ian, Cao, Michelle, Chakrabarti, Anannya, Chauhan, Deepa, Chauhan, Manisha, Chenevix‐Trench, Georgia, Christian, Alice, Cohen, Paul, Colley, Alison, Crook, Ashley, Cui, James, Courtney, Eliza, Cummings, Margaret, and Dawson, Sarah‐Jane

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Women's Health, Breast Cancer, Clinical Research, Prevention, Cancer, Female, Humans, Breast Neoplasms, Checkpoint Kinase 2, Genetic Predisposition to Disease, Germ-Line Mutation, Heterozygote, Proportional Hazards Models, CHEK2 c.1100delC germline genetic variant, contralateral breast cancer risk, radiotherapy, survival, systemic treatment, NBCS Collaborators, ABCTB Investigators, kConFab Investigators, Biochemistry and Cell Biology, Oncology and carcinogenesis
Abstract

BackgroundBreast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers.AimTo assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS.MethodsAnalyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death.ResultsThere was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)].ConclusionSystemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.

Published
2023

33. An integrated single-cell RNA-seq map of human neuroblastoma tumors and preclinical models uncovers divergent mesenchymal-like gene expression programs

Author

Chapple, Richard H., Liu, Xueying, Natarajan, Sivaraman, Alexander, Margaret I. M., Kim, Yuna, Patel, Anand G., LaFlamme, Christy W., Pan, Min, Wright, William C., Lee, Hyeong-Min, Zhang, Yinwen, Lu, Meifen, Koo, Selene C., Long, Courtney, Harper, John, Savage, Chandra, Johnson, Melissa D., Confer, Thomas, Akers, Walter J., Dyer, Michael A., Sheppard, Heather, Easton, John, and Geeleher, Paul

Published
2024
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41. The CompactLight Design Study

Author

D’Auria, G., Adli, E., Aicheler, M., Aksoy, A., Alesini, D., Apsimon, R., Arnsberg, J., Auchettl, R., Bainbridge, A., Balazs, K., Bantekas, D., Bedolla, J., Behtouei, M., Bellaveglia, M., vd Berg, M., Bernhard, A., Bignami, A., Breitenbach, M., Breukers, M., Burt, G., Cai, J., Calvi, M., Cardelli, F., Carpanese, M., Cortes, H. M. Castaneda, Castilla, A., Cianchi, A., Clarke, J., Cowie, L., Croia, M., Cross, A., Danailov, M., Dattoli, G., Deleval, S., Mitri, S. Di, Diomede, M., Dowd, R., Dunning, D., Easton, J., Fang, W., Fatehi, S., Faus-Golfe, A., Ferianis, M., Ferrario, M., Ficcadenti, L., Gallo, A., Gazis, E., Gazis, N., Geometrante, R., Gethmann, J., Gioppo, R., Giribono, A., González-Iglesias, D., Goryashko, V., Grohmann, S., Gu, Q., Han, Y., Hinton, A., Hobi, A., Hoekstra, R., Huang, X., Jacewicz, M., Jones, J., Kaertner, F., Karagiannaki, A., Kokole, M., Kotitsa, R., Kotsopoulos, D., Krasch, B., Latina, A., Lepercq, P., Liu, X., Lucas, T. G., Luiten, O. J., Maheshwari, M., Mahnic, J., Mak, A., Marcos, J., Marin, E., Marinov, K., Martínez, B. G., Mercier, B., Migliorati, M., Milharcic, T., Mostacci, A., Mu noz, R., Musat, V., Mutsaers, P. H. A., Nergiz, Z., Nguyen, F., Nix, L., Palumbo, L., Parodi, M., Pavlica, R., Pellegrino, L., Pereira, D. E., Perez, F., Petralia, A., Piersanti, L., Pockar, J., Pramatari, K., Priem, H., Primozic, U., Rassool, R., Reiche, S., Revilak, P., Richter, S. C., Rochow, R., Rossi, C., Salén, P., Schmidt, T., Schoerling, D., Schulte, D., Scifo, J., Sheehy, S., Shepherd, B., Spataro, B., Stapnes, S., Stragier, X. F. D., Syratchev, I., Tabacco, C., Tan, J., Tanke, E., Taylor, G., Telahi, I., Thompson, N., Trachanas, E., Tzanetou, K. S., Vaccarezza, C., Vainola, J., Vannozzi, A., Volpi, M., Wang, C., Williams, P., Wu, X., Wuensch, W., Yap, J., Zangrando, M., Zhang, K., Zhang, L., Zhao, Y., Zhao, Z., and Zhu, D.

Published
2024
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43. Factorization in Additive Monoids of Evaluation Polynomial Semirings

Author

Ajran, Khalid, Bringas, Juliet, Li, Bangzheng, Singer, Easton, and Tirador, Marcos

Subjects
Mathematics - Commutative Algebra, Primary: 13A05, 16Y60, Secondary: 06F05, 11R09
Abstract

For a positive real $\alpha$, we can consider the additive submonoid $M$ of the real line that is generated by the nonnegative powers of $\alpha$. When $\alpha$ is transcendental, $M$ is a unique factorization monoid. However, when $\alpha$ is algebraic, $M$ may not be atomic, and even when $M$ is atomic, it may contain elements having more than one factorization (i.e., decomposition as a sum of irreducibles). The main purpose of this paper is to study the phenomenon of multiple factorizations inside $M$. When $\alpha$ is algebraic but not rational, the arithmetic of factorizations in $M$ is highly interesting and complex. In order to arrive to that conclusion, we investigate various factorization invariants of $M$, including the sets of lengths, sets of Betti elements, and catenary degrees. Our investigation gives continuity to recent studies carried out by Chapman, et al. in 2020 and by Correa-Morris and Gotti in 2022., Comment: 18 pages

Published
2023

44. Carbapenemase-producing enterobacterales colonisation status does not lead to more frequent admissions: a linked patient study

Author

Michael J. Lydeamore, Tjibbe Donker, David Wu, Claire Gorrie, Annabelle Turner, Marion Easton, Daneeta Hennessy, Nicholas Geard, Benjamin P. Howden, Ben S. Cooper, Andrew Wilson, Anton Y. Peleg, and Andrew J. Stewardson

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Hospitals in any given region can be considered as part of a network, where facilities are connected to one another – and hospital pathogens potentially spread – through the movement of patients between them. We sought to describe the hospital admission patterns of patients known to be colonised with carbapenemase-producing Enterobacterales (CPE), and compare them with CPE-negative patient cohorts, matched on comorbidity information. Methods We performed a linkage study in Victoria, Australia, including datasets with notifiable diseases (CPE notifications) and hospital admissions (admission dates and diagnostic codes) for the period 2011 to 2020. Where the CPE notification date occurred during a hospital admission for the same patient, we identified this as the ‘index admission’. We determined the number of distinct health services each patient was admitted to, and time to first admission to a different health service. We compared CPE-positive patients with four cohorts of CPE-negative patients, sampled based on different matching criteria. Results Of 528 unique patients who had CPE detected during a hospital admission, 222 (42%) were subsequently admitted to a different health service during the study period. Among these patients, CPE diagnosis tended to occur during admission to a metropolitan public hospital (86%, 190/222), whereas there was a greater number of metropolitan private (23%, 52/222) and rural public (18%, 39/222) hospitals for the subsequent admission. Median time to next admission was 4 days (IQR, 0–75 days). Admission patterns for CPE-positive patients was similar to the cohort of CPE-negative patients matched on index admission, time period, and age-adjusted Charlson comorbidity index. Conclusions Movement of CPE-positive patients between health services is not a rare event. While the most common movement is from one public metropolitan health service to another, there is also a trend for movement from metropolitan public hospitals into private and rural hospitals. After accounting for clinical comorbidities, CPE colonisation status does not appear to impact on hospital admission frequency or timing. These findings support the potential utility of a centralised notification and outbreak management system for CPE positive patients.

Published
2024
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45. Mice integrate conspecific and contextual information in forming social episodic-like memories under spontaneous recognition task conditions

Author

T. W. Ross, S. L. Poulter, C. Lever, and A. Easton

Subjects
Medicine, Science
Abstract

Abstract The ability to remember unique past events (episodic memory) may be an evolutionarily conserved function, with accumulating evidence of episodic-(like) memory processing in rodents. In humans, it likely contributes to successful complex social networking. Rodents, arguably the most used laboratory models, are also rather social animals. However, many behavioural paradigms are devoid of sociality, and commonly-used social spontaneous recognition tasks (SRTs) are open to non-episodic strategies based upon familiarity. We address this gap by developing new SRT variants. Here, in object-in-context SRTs, we asked if context could be specified by the presence/absence of either a conspecific (experiment 1) or an additional local object (experiment 2). We show that mice readily used the conspecific as contextual information to distinguish unique episodes in memory. In contrast, no coherent behavioural response emerged when an additional object was used as a potential context specifier. Further, in a new social conspecific-in-context SRT (experiment 3) where environment-based change was the context specifier, mice preferably explored a more recently-seen familiar conspecific associated with contextual mismatch, over a less recently-seen familiar conspecific presented in the same context. The results argue that, in incidental SRT conditions, mice readily incorporate conspecific cue information into episodic-like memory. Thus, the tasks offer different ways to assess and further understand the mechanisms at work in social episodic-like memory processing.

Published
2024
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46. An integrated single-cell RNA-seq map of human neuroblastoma tumors and preclinical models uncovers divergent mesenchymal-like gene expression programs

Author

Richard H. Chapple, Xueying Liu, Sivaraman Natarajan, Margaret I. M. Alexander, Yuna Kim, Anand G. Patel, Christy W. LaFlamme, Min Pan, William C. Wright, Hyeong-Min Lee, Yinwen Zhang, Meifen Lu, Selene C. Koo, Courtney Long, John Harper, Chandra Savage, Melissa D. Johnson, Thomas Confer, Walter J. Akers, Michael A. Dyer, Heather Sheppard, John Easton, and Paul Geeleher

Subjects
Biology (General), QH301-705.5, Genetics, QH426-470
Abstract

Abstract Background Neuroblastoma is a common pediatric cancer, where preclinical studies suggest that a mesenchymal-like gene expression program contributes to chemotherapy resistance. However, clinical outcomes remain poor, implying we need a better understanding of the relationship between patient tumor heterogeneity and preclinical models. Results Here, we generate single-cell RNA-seq maps of neuroblastoma cell lines, patient-derived xenograft models (PDX), and a genetically engineered mouse model (GEMM). We develop an unsupervised machine learning approach (“automatic consensus nonnegative matrix factorization” (acNMF)) to compare the gene expression programs found in preclinical models to a large cohort of patient tumors. We confirm a weakly expressed, mesenchymal-like program in otherwise adrenergic cancer cells in some pre-treated high-risk patient tumors, but this appears distinct from the presumptive drug-resistance mesenchymal programs evident in cell lines. Surprisingly, however, this weak-mesenchymal-like program is maintained in PDX and could be chemotherapy-induced in our GEMM after only 24 h, suggesting an uncharacterized therapy-escape mechanism. Conclusions Collectively, our findings improve the understanding of how neuroblastoma patient tumor heterogeneity is reflected in preclinical models, provides a comprehensive integrated resource, and a generalizable set of computational methodologies for the joint analysis of clinical and pre-clinical single-cell RNA-seq datasets.

Published
2024
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47. In situ observation and reduction of hot-cracks in laser additive manufacturing

Author

Yunhui Chen, Duyao Zhang, Patrick O’Toole, Dong Qiu, Marc Seibold, Klaus. Schricker, Jean-Pierre Bergmann, Alexander Rack, and Mark Easton

Subjects
Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract

Abstract Cracking during Laser Additive Manufacturing is a problem for many higher-strength aluminium alloys, including AA6061. Here, we used a pulsed laser with ramp-down power modulation to improve the cracking resistance by about 50% compared to the use of a rectangular pulsed laser. Using synchrotron in situ X-ray imaging at 100,000 images s −1, ground truth data was obtained about changes in melt pool geometry, solidification rate, and thermal gradients were calculated. An analytical hot cracking model was developed to show that these changes lead to a decreased hot tear susceptibility. Therefore, laser pulse modulation can be an effective tool to reduce crack susceptibility of alloys. More fundamentally, the results demonstrate that modifying thermal conditions provides a pathway to crack elimination in LAM and the model established in our study sets the foundation for further complex laser manipulation in modifying the printability and resulting mechanical properties of hard-to-process alloys in Laser Additive Manufacturing.

Published
2024
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48. First observation of rotational bands in the nucleus 231U

Author

Roux, D. G., Bark, R. A., Lawrie, E. A., Lawrie, J. J., Ntshangase, S. S., Dinoko, T. S., Easton, J. L., Jones, P., Kheswa, B. V., Khumalo, N. A., Majola, S. N. T., Masiteng, L. P., Negi, D., Noncolela, S. P., Ndayishimye, J., Sharpey-Schafer, J. F., Shirinda, O., and Uwitonze, P. C.

Published
2024
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49. Corrigendum

Author

Beach, Callum, MacLean, David, Majorova, Dominika, Melemenidis, Stavros, Nambiar, Dhanya K., Kim, Ryan K., Valbuena, Gabriel N., Guglietta, Silvia, Krieg, Carsten, Darvish-Damavandi, Mahnaz, Suwa, Tatsuya, Easton, Alistair, Hillson, Lily V.S., McCulloch, Ashley K., McMahon, Ross K., Pennel, Kathryn, Edwards, Joanne, O'Cathail, Sean M., Roxburgh, Campbell S., Domingo, Enric, Moon, Eui Jung, Jiang, Dadi, Jiang, Yanyan, Zhang, Qingyang, Koong, Albert C., Woodruff, Trent M., Graves, Edward E., Maughan, Tim, Buczacki, Simon J.A., Stucki, Manuel, Le, Quynh-Thu, Leedham, Simon J., Giaccia, Amato J., and Olcina, Monica M.

Abstract

Original citation: J Clin Invest. 2023;133(23):e168277. https://doi.org/10.n72/JCI168277. During the preparation of this manuscript, the dose for PMX205 used for in vitro experiments was stated incorrectly in the legend for Figure [...]

Published
2024
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50. Ovarian cancer pathology characteristics as predictors of variant pathogenicity in BRCA1 and BRCA2

Author

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.

Published
2023

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