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A multi-class ramp metering and routing control scheme to reduce congestion and traffic emissions in freeway networks

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IFAC-PapersOnLine 2016年第3期49卷 329-334页

作者： Pasquale, C. Sacone, S. Siri, S. De Schutter, B. Department of Informatics Bioengineering Robotics and Systems Engineering University of Genova Italy Delft Center for Systems and Control Delft University of Technology Netherlands

In this paper, a multi-class and multi-objective combined ramp metering and routing control strategy is proposed to improve performance in freeway traffic networks. The control strategy is of the multi-class type, i.e. different classes of vehicles are taken into account, so that specific control policies can be devised for each class. Moreover, ramp metering and route guidance are properly coordinated in order to reduce the total travel time and the total emissions in the freeway system in a balanced way. The controller proposed in the paper is of the predictive feedback type, i.e. the control computed at each time step depends on the measured system state and on the prediction of the system evolution, considering both a traffic and an emission model. Some simulation results are presented showing the effectiveness of the proposed control scheme. © 2016

关键词： Traffic congestion Highway traffic control Network routing Travel time control strategies Different class Freeway networks Improve performance Measured system System evolution Total emissions Traffic emissions

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The DREM Approach for Chaotic Oscillators Parameter Estimation with Improved Performance

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IFAC-PapersOnLine 2017年第1期50卷 7027-7031页

作者： Gromov V.S. Borisov O.I. Pyrkin A.A. Bobtsov A.A. Kolyubin S.A. Aranovskiy S.V. Department of Control Systems and Informatics ITMO University Kronverkskiy pr. 49 St. Petersburg 197101 Russian Federation Laboratory “Control of Complex Systems” Institute of Problems of Mechanical Engineering V.O. Bolshoj pr. 61 St. Petersburg 199178 Russian Federation CentraleSupélec - IETR Avenue de la Boulaie Cesson-Sévigné 35576 France

In this paper we address the problem of parameter estimation performance enhancement for Duffing-like chaotic oscillator with parametric uncertainties. The Dynamic Regressor Extension and Mixing (DREM) approach, which has been recently proposed by the authors, is proven to be a powerful tool in transients improvement; however, it was never applied before for chaotic systems. Here we elaborate on how the DREM approach can be applied for the parameter reconstruction problem of chaotic signal generator used in the data transmitting scenario. The set of numerical examples illustrates the benefits of the proposed approach. © 2017

关键词： Chaotic behavior Observers Transmitters

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Cost-benefit analysis game for efficient storage allocation in cloud-centric Internet of Things systems: A game theoretic perspective 15

Cost-benefit analysis game for efficient storage allocation ...

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15th IFIP/IEEE International Symposium on Integrated Network and Service Management, IM 2017

作者： Skourletopoulos, Georgios Mavromoustakis, Constandinos X. Mastorakis, George Sahalos, John N. Batalla, Jordi Mongay Dobre, Ciprian Department of Computer Science University of Nicosia Nicosia Cyprus Department of Informatics Engineering Technological Educational Institute of Crete Heraklion Crete Greece Department of Physics Aristotle University of Thessaloniki Thessaloniki Greece National Institute of Telecommunications and Warsaw University of Technology Szachowa Str. 1 and Nowowiejska Str. 15/19 Warsaw Poland Department of Computer Science and Engineering Faculty of Automatic Control and Computers University Politehnica of Bucharest Bucharest Romania

ISBN: (纸本)9783901882890

The advances in Internet of Everything (IoE) and the market-oriented cloud computing have provided opportunities to resolve the challenges caused by the Internet of Things (IoT) infrastructure virtualization, capacity planning, data storage or complexity. The volume and types of IoT data motivate the need for a data storage framework towards the integration of both structured and unstructured data. In this paper, we propose a novel game theoretic technique for efficient and dynamic storage allocation in cloud-centric IoT systems. The benefit maximization problem is formulated as a cost-benefit analysis game investigating the storage capacity currently used in the cloud. In view of each player's strategy to lease additional storage capacity, the game property is analyzed and we prove that the game always admits a pure strategy Nash equilibrium. Since the player's decision affects the level of benefit maximization, we elaborate on a cost-optimal storage allocation incentive mechanism, which scales effectively once non-linear or linear demand for storage capacity occurs, towards achieving optimal leasing conditions on cloud storage and computing capacity level. The experimental validation tests prove the effectiveness of the proposed game theoretic approach allocating the requests for more storage capacity in a cost-effective manner, which achieves to maximize the benefits. © 2017 IFIP.

关键词： Distributed cloud

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Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990–2019, for 204 countries and territories: the Global Burden of Diseases Study 2019

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The Lancet HIV 2021年第10期8卷 e633-e651页

作者： Jahagirdar, Deepa Walters, Magdalene K. Novotney, Amanda Brewer, Edmond D. Frank, Tahvi D. Carter, Austin Biehl, Molly H. Abbastabar, Hedayat Abhilash, E.S. Abu-Gharbieh, Eman Abu-Raddad, Laith Jamal Adekanmbi, Victor Adeyinka, Daniel Adedayo Adnani, Qorinah Estiningtyas Sakilah Afzal, Saira Aghababaei, Soodabeh Ahinkorah, Bright Opoku Ahmad, Sajjad Ahmadi, Keivan Ahmadi, Sepideh Ahmadpour, Ehsan Ahmed, Muktar Beshir Rashid, Tarik Ahmed Salih, Yusra Ahmed Aklilu, Addis Akram, Tayyaba Akunna, Chisom Joyqueenet Al Hamad, Hanadi Alahdab, Fares Alanezi, Fahad Mashhour Aleksandrova, Ekaterina A. Alene, Kefyalew Addis Ali, Liaqat Alipour, Vahid Almustanyir, Sami Alvis-Guzman, Nelson Ameyaw, Edward Kwabena Amu, Hubert Andrei, Catalina Liliana Andrei, Tudorel Anvari, Davood Arabloo, Jalal Aremu, Olatunde Arulappan, Judie Atnafu, Desta Debalkie Quintanilla, Beatriz Paulina Ayala Ayza, Muluken Altaye Azari, Samad Darshan, B.B. Banach, Maciej Bärnighausen, Till Winfried Barra, Fabio Barrow, Amadou Basu, Sanjay Bazargan-Hejazi, Shahrzad Belay, Habtamu Gebrehana Berheto, Tezera Moshago Bezabhe, Woldesellassie Mequanint Bezabih, Yihienew Mequanint Bhagavathula, Akshaya Srikanth Bhardwaj, Nikha Bhardwaj, Pankaj Bhattacharyya, Krittika Bibi, Sadia Bijani, Ali Bisignano, Catherine Bolarinwa, Obasanjo Afolabi Boloor, Archith Boltaev, Azizbek A. Briko, Nikolay Ivanovich Buonsenso, Danilo Burkart, Katrin Butt, Zahid A. Cao, Chao Charan, Jaykaran Chatterjee, Souranshu Chattu, Soosanna Kumary Chattu, Vijay Kumar Choudhari, Sonali Gajanan Chu, Dinh-Toi Couto, Rosa A.S. Cowden, Richard G. Dachew, Berihun Assefa Dadras, Omid Dagnew, Amare Belachew Dahlawi, Saad M.A. Dai, Xiaochen Dandona, Lalit Dandona, Rakhi das Neves, José Degenhardt, Louisa Demeke, Feleke Mekonnen Desta, Abebaw Alemayehu Deuba, Keshab Dhamnetiya, Deepak Dhungana, Govinda Prasad Dianatinasab, Mostafa Diaz, Daniel Djalalinia, Shirin Doan, Linh Phuong Dorostkar, Fariba Edinur, Hisham Atan Effiong, Andem Eftekharzadeh, Sahar El Sayed Zaki, Maysaa Elayedath, Rajesh Elhadi, Institute for Health Metrics and Evaluation University of Washington Seattle WA United States Department of Health Metrics Sciences School of Medicine University of Washington Seattle WA United States Division of Allergy and Infectious Diseases University of Washington Seattle WA United States Department of Global Health University of Washington Seattle WA United States School of Social Work University of Washington Seattle WA United States Department of Medicine University of Washington Seattle WA United States Vagelos College of Physicians and Surgeones Columbia University Medical Center New York NY United States Division of Data Analytics and Delivery for Impact WHO Geneva Switzerland Advanced Diagnostic and Interventional Radiology Research Centre Tehran University of Medical Sciences Tehran Iran Multiple Sclerosis Research Centre Tehran University of Medical Sciences Tehran Iran School of Public Health Tehran University of Medical Sciences Tehran Iran Department of Epidemiology and Biostatistics Tehran University of Medical Sciences Tehran Iran Paediatric Chronic Kidney Disease Research Centre Tehran University of Medical Sciences Tehran Iran Department of Psychiatry Tehran University of Medical Sciences Tehran Iran Metabolomics and Genomics Research Centre Tehran University of Medical Sciences Tehran Iran Sina Trauma and Surgery Research Centre Tehran University of Medical Sciences Tehran Iran Research Centre for Immunodeficiencies Tehran University of Medical Sciences Tehran Iran Non-Communicable Diseases Research Centre Tehran University of Medical Sciences Tehran Iran Department of Botany Sree Narayana Guru College Chelannur Kozhikode India Clinical Sciences Department University of Sharjah Sharjah United Arab Emirates Mass Communication Department University of Sharjah Sharjah United Arab Emirates Department of Health-Care Policy and Research Weill Cornell Medical College in Qatar Doha Qatar Department of Population Medicine Ca

Background: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. Methods: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). Findings: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1–38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78–0·91) per female living with HIV in 2019, 0·99 male infections (0·91–1·10) for every female infection, and 1·02 male deaths (0·95–1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58–35·43, and a 39·66% decrease in deaths, 36·49–42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05–0·06) and the global incidence-to-mortality ratio was

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Subnational mapping of HIV incidence and mortality among individuals aged 15–49 years in sub-Saharan Africa, 2000–18: a modelling study

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The Lancet HIV 2021年第6期8卷 e363-e375页

作者： Sartorius, Benn VanderHeide, John D. Yang, Mingyou Goosmann, Erik A. Hon, Julia Haeuser, Emily Cork, Michael A. Perkins, Samantha Jahagirdar, Deepa Schaeffer, Lauren E. Serfes, Audrey L. LeGrand, Kate E. Abbastabar, Hedayat Abebo, Zeleke Hailemariam Abosetugn, Akine Eshete Abu-Gharbieh, Eman Accrombessi, Manfred Mario Kokou Adebayo, Oladimeji M. Adegbosin, Adeyinka Emmanuel Adekanmbi, Victor Adetokunboh, Olatunji O. Adeyinka, Daniel Adedayo Ahinkorah, Bright Opoku Ahmadi, Keivan Ahmed, Muktar Beshir Akalu, Yonas Akinyemi, Oluwaseun Oladapo Akinyemi, Rufus Olusola Aklilu, Addis Akunna, Chisom Joyqueenet Alahdab, Fares Al-Aly, Ziyad Alam, Noore Alamneh, Alehegn Aderaw Alanzi, Turki M. Alemu, Biresaw Wassihun Alhassan, Robert Kaba Ali, Tilahun Alipour, Vahid Amini, Saeed Ancuceanu, Robert Ansari, Fereshteh Anteneh, Zelalem Alamrew Anvari, Davood Anwer, Razique Appiah, Seth Christopher Yaw Arabloo, Jalal Asemahagn, Mulusew A. Asghari Jafarabadi, Mohammad Asmare, Wondwossen Niguse Atnafu, Desta Debalkie Atout, Maha Moh'd Wahbi Atreya, Alok Ausloos, Marcel Awedew, Atalel Fentahun Ayala Quintanilla, Beatriz Paulina Ayanore, Martin Amogre Aynalem, Yared Asmare Ayza, Muluken Altaye Azari, Samad Azene, Zelalem Nigussie Babar, Zaheer-Ud-Din Baig, Atif Amin Balakrishnan, Senthilkumar Banach, Maciej Bärnighausen, Till Winfried Basu, Sanjay Bayati, Mohsen Bedi, Neeraj Bekuma, Tariku Tesfaye Bezabhe, Woldesellassie M. Mequanint Bhagavathula, Akshaya Srikanth Bhardwaj, Pankaj Bhattacharyya, Krittika Bhutta, Zulfiqar A. Bibi, Sadia Bikbov, Boris Birhan, Tsegaye Adane Bitew, Zebenay Workneh Bockarie, Moses John Boloor, Archith Brady, Oliver J. Bragazzi, Nicola Luigi Briko, Andrey Nikolaevich Briko, Nikolay Ivanovich Burugina Nagaraja, Sharath Butt, Zahid A. Cárdenas, Rosario Carvalho, Felix Charan, Jaykaran Chatterjee, Souranshu Chattu, Soosanna Kumary Chattu, Vijay Kumar Chowdhury, Mohiuddin Ahsanul Kabir Chu, Dinh-Toi Cook, Aubrey J. Cormier, Natalie Maria Cowden, Richard G. Culquichicon, Carlos Dagnew, Baye Dahlawi, Saad M.A. D Centre for Tropical Medicine and Global Health Nuffield Department of Medicine University of Oxford Oxford United Kingdom Malaria Atlas Project University of Oxford Oxford United Kingdom The George Institute for Global Health University of Oxford Oxford United Kingdom Department of Health Metrics Sciences School of Medicine University of Washington Seattle WA United States Institute for Health Metrics and Evaluation University of Washington Seattle WA United States Department of Global Health University of Washington Seattle WA United States Department of Medicine University of Washington Seattle WA United States Insights Program Bill and Melinda Gates Foundation Seattle WA United States Global Programs Medical Teams International Seattle WA United States Department of Pediatric Newborn Medicine Brigham and Women's Hospital Boston MA United States Advanced Diagnostic and Interventional Radiology Research Center Tehran University of Medical Sciences Tehran Iran Multiple Sclerosis Research Center Tehran University of Medical Sciences Tehran Iran Department of Epidemiology and Biostatistics Tehran University of Medical Sciences Tehran Iran Pediatric Chronic Kidney Disease Research Center Tehran University of Medical Sciences Tehran Iran Department of Environmental Health Engineering Tehran University of Medical Sciences Tehran Iran Metabolomics and Genomics Research Center Tehran University of Medical Sciences Tehran Iran Research Center for Immunodeficiencies Tehran University of Medical Sciences Tehran Iran Department of Public Health Arba Minch University Arba Minch Ethiopia Department of Medical Laboratory Sciences Arba Minch University Arba Minch Ethiopia College of Medicine and Health Science Arba Minch University Arba Minch Ethiopia Department of Nursing Arba Minch University Arba Minch Ethiopia Department of Biomedical Sciences Arba Minch University Arba Minch Ethiopia Department of Public Health Debre Berhan University Debre Brehan

Background: High-resolution estimates of HIV burden across space and time provide an important tool for tracking and monitoring the progress of prevention and control efforts and assist with improving the precision and efficiency of targeting efforts. We aimed to assess HIV incidence and HIV mortality for all second-level administrative units across sub-Saharan Africa. Methods: In this modelling study, we developed a framework that used the geographically specific HIV prevalence data collected in seroprevalence surveys and antenatal care clinics to train a model that estimates HIV incidence and mortality among individuals aged 15–49 years. We used a model-based geostatistical framework to estimate HIV prevalence at the second administrative level in 44 countries in sub-Saharan Africa for 2000–18 and sought data on the number of individuals on antiretroviral therapy (ART) by second-level administrative unit. We then modified the Estimation and Projection Package (EPP) to use these HIV prevalence and treatment estimates to estimate HIV incidence and mortality by second-level administrative unit. Findings: The estimates suggest substantial variation in HIV incidence and mortality rates both between and within countries in sub-Saharan Africa, with 15 countries having a ten-times or greater difference in estimated HIV incidence between the second-level administrative units with the lowest and highest estimated incidence levels. Across all 44 countries in 2018, HIV incidence ranged from 2·8 (95% uncertainty interval 2·1–3·8) in Mauritania to 1585·9 (1369·4–1824·8) cases per 100 000 people in Lesotho and HIV mortality ranged from 0·8 (0·7–0·9) in Mauritania to 676·5 (513·6–888·0) deaths per 100 000 people in Lesotho. Variation in both incidence and mortality was substantially greater at the subnational level than at the national level and the highest estimated rates were accordingly higher. Among second-level administrative units, Guijá District, Gaza Province, Mozambique,

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Networked human motion capture system based on quaternion navigation 11

Networked human motion capture system based on quaternion na...

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11th International Conference on Body Area Networks, BODYNETS 2016

作者： Li, Jie Wang, Zhe-Long Zhao, Hongyu Gravina, Raffaele Fortino, Giancarlo Jiang, Yongmei Tang, Kai School of Control Science and Engineering Dalian University of Technology Dalian China Department of Informatics Modeling Electronics and Systems University of Calabria Rende Italy Second Affiliated Hospital Dalian Medical University Dalian China First Affiliated Hospital Dalian Medical University Dalian China 87036 Italy

In this paper, from the perspective of human ergonomics, we analyze the movement of the joints in the process of human body movements, and we establish a dynamic model according to the human skeleton structure. On this basis, from the rigid body dynamics point of view, combined with the principle of inertial navigation, a body sensor network based on MEMS inertial sensors is built to capture human body motion in real time. On the basis of space trajectory of human body movement and traditional human motion solution strategy, a human motion solution strategy based on particle filter fusion solution is proposed to realize the prediction of human motion analysis. Therefore, we evaluate the performance of the designed system by comparing with the real motion. Finally, in order to verify the human motion data, the motion capture data verification platforms are established. Experimental results show that the proposed joint attitude solution algorithm can achieve a relatively smooth tracking effect and provides a certain reference value. © 2017 EAI.

关键词： Inertial navigation systems

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Pupillary Reactivity to Non-Photorealistic Rendering: A Case Study of Immersion in 3D Cinema

Pupillary Reactivity to Non-Photorealistic Rendering: A Case...

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International Conference on 3D Imaging (IC3D)

作者： Victor FAJNZYLBER Samuel MADARIAGA Rafael DEL VILLAR Pedro MALDONADO Diego Vargas Aria SERRA Milan MAGDICS Mateu SBERT Communication and Imaging Institute University of Chile Departamento de Neurociencia & Biomedical Neuroscience Institute University of Chile National School of Higher Studies Campus Morelia National Autonomous University of Mexico Institute of Informatics and Applications & Graphics and Imaging Laboratory Girona University Department of Control Engineering and Information Technology Budapest University of Technology and Economics School of Computer Science and Technology Tianjin University

ISBN: (纸本)9781538675915;9781538675908

The aim of our research is to build an empirical indicator of cinematic immersion based on ocular data. We study immersion as a gradual and adaptive process of corporal involvement in the cinematic experience. To study its temporal evolution, we analyze correlations between the film and the ocular response, in its attentional aspects (what do we see?) and pupillary aspects (how do we react?). To understand in what ways post-production can favor immersion, we are interested in studying the pupil reactivity to visual attributes of the film: the visual abstraction of a non-photorealistic rendering (NPR) post-production and the optical hyperrealism of stereoscopy. We expect that our results could be useful for conceiving new NPR tools for 3D films and innovative post-production strategies for virtual reality.

关键词： Motion pictures Visualization Three-dimensional displays Stereo image processing Videos Rendering (computer graphics) Correlation

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Predictive control of differential drive mobile robot considering dynamics and kinematics 30

Predictive control of differential drive mobile robot consid...

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30th European Conference on Modelling and Simulation, ECMS 2016

作者： Rahul, Sharma K. Honc, Daniel Dušek, František Department of Process Control Faculty of Electrical Engineering and Informatics University of Pardubice Czech Republic

ISBN: (纸本)9780993244025

The paper deals with trajectory tracking of the differential drive robot with a mathematical model governing dynamics and kinematics. Motor dynamics and chassis dynamics are considered for deriving a linear state-space dynamic model. Basic nonlinear kinematic equations are linearized into a successively linearized state-space model. The dynamic and kinematic models are augmented to derive a single state-space linear model. The deviation variables are reference variables which are variables of an ideal robot following a reference trajectory which can be pre-calculated. Reference tracking is achieved by model predictive control of supply voltage of both the drive motors by considering constraints on controlled variables and manipulated variables. Simulation results are provided to demonstrate the performance of proposed control strategy in the MATLAB simulation environment. © ECMS Thorsten Claus, Frank Herrmann, Michael Manitz, Oliver Rose (Editors).

关键词： Mobile robots

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IAE based tuning of controller anti-windup schemes for first order plus dead-time system

IAE based tuning of controller anti-windup schemes for first...

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International Conference on Process control (PC)

作者： Jaroslav Bŭsek Tomáš Vyhlídal Pavel Zítek Department of Instrumentation and Control Engineering Czech Technical University in Prague Czech Republic Czech Institute of Informatics Czech Technical University in Prague Czech Republic

The paper is focused on IAE based tuning the anti-windup feedback in a controller of a first order plus dead time model. The problem is addressed to two types of controllers, finite order PI and infinite order Internal Model controller (IMC) with the delay compensation. For the PI a classical finite order feedback known as back-calculation method is utilized, whereas for the IMC, a novel functional feedback is proposed. For both the cases, the feedback setting is optimized with respect to minimizing the IAE criterion. The analysis is performed on a dimensionless form of the model so that the results are valid to a broad class of systems. For both PI and IMC, the `optimal' dynamics of the anti-windup loop is of first order with the time constant being close to the time constant of the plant model.

关键词： Mathematical model Tuning Delay effects Windup Delays Optimization Process control

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Analysis of more than 400,000 women provides case-control evidence for BRCA1 and BRCA2 variant classification

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Nature Communications 2025年第1期16卷 1-18页

作者： Zanti, Maria O’Mahony, Denise G. Parsons, Michael T. Dorling, Leila Dennis, Joe Boddicker, Nicholas J. Chen, Wenan Hu, Chunling Naven, Marc Yiangou, Kristia Ahearn, Thomas U. Ambrosone, Christine B. Andrulis, Irene L. Antoniou, Antonis C. Auer, Paul L. Baynes, Caroline Bodelon, Clara Bogdanova, Natalia V. Bojesen, Stig E. Bolla, Manjeet K. Brantley, Kristen D. Camp, Nicola J. Campbell, Archie Castelao, Jose E. Cessna, Melissa H. Chang-Claude, Jenny Chen, Fei Chenevix-Trench, Georgia Kristensen, Vessela N. Conroy, Don M. Czene, Kamila De Nicolo, Arcangela Domchek, Susan M. Dörk, Thilo Dunning, Alison M. Eliassen, A. Heather Evans, D. Gareth Fasching, Peter A. Figueroa, Jonine D. Flyger, Henrik Gago-Dominguez, Manuela García-Closas, Montserrat Glendon, Gord González-Neira, Anna Grassmann, Felix Hadjisavvas, Andreas Haiman, Christopher A. Hamann, Ute Hart, Steven N. Hartman, Mikael B. A. Ho, Weang-Kee Hodge, James M. Hoppe, Reiner Howell, Sacha J. Jakubowska, Anna Khusnutdinova, Elza K. Ko, Yon-Dschun Kraft, Peter Kristensen, Vessela N. Lacey, James V. Li, Jingmei Lim, Geok Hoon Lindström, Sara Lophatananon, Artitaya Luccarini, Craig Mannermaa, Arto Martinez, Maria Elena Mavroudis, Dimitrios Milne, Roger L. Muir, Kenneth Nathanson, Katherine L. Nuñez-Torres, Rocio Obi, Nadia Olson, Janet E. Palmer, Julie R. Panayiotidis, Mihalis I. Patel, Alpa V. Pharoah, Paul D. P. Polley, Eric C. Rashid, Muhammad U. Ruddy, Kathryn J. Saloustros, Emmanouil Sawyer, Elinor J. Schmidt, Marjanka K. Southey, Melissa C. Tan, Veronique Kiak-Mien Teo, Soo Hwang Teras, Lauren R. Torres, Diana Trentham-Dietz, Amy Truong, Thérèse Vachon, Celine M. Wang, Qin Weitzel, Jeffrey N. Yadav, Siddhartha Yao, Song Zirpoli, Gary R. Cline, Melissa S. Devilee, Peter Tavtigian, Sean V. Goldgar, David E. Couch, Fergus J. Easton, Douglas F. Spurdle, Amanda B. Michailidou, Kyriaki Biostatistics Unit The Cyprus Institute of Neurology & Genetics Nicosia Cyprus Department of Medical Genetics Oslo University Hospital Oslo Norway Population Health Program QIMR Berghofer Medical Research Institute Brisbane QLD Australia Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care University of Cambridge Cambridge United Kingdom Department of Quantitative Health Sciences Division of Computational Biology Mayo Clinic Rochester MN United States Department of Laboratory Medicine and Pathology Mayo Clinic Rochester MN United States Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Department of Health and Human Services Bethesda MD United States Department of Cancer Prevention and Control Roswell Park Comprehensive Cancer Institute Buffalo NY United States Fred A. Litwin Center for Cancer Genetics Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital Toronto Ontario Canada Department of Molecular Genetics University of Toronto Toronto Ontario Canada Division of Biostatistics Data Science Institute and Cancer Center Medical College of Wisconsin Milwaukee WI United States Centre for Cancer Genetic Epidemiology Department of Oncology University of Cambridge Cambridge United Kingdom Department of Population Science American Cancer Society Atlanta GA United States Radiation Oncology Research Unit Hannover Medical School Hannover Germany Copenhagen General Population Study Herlev and Gentofte Hospital Copenhagen University Hospital Herlev Denmark Department of Clinical Biochemistry Herlev and Gentofte Hospital Copenhagen University Hospital Herlev Denmark Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark Department of Medical Oncology Dana-Farber Cancer Institute Boston MA United States Department of Internal Medicine and Huntsman Cancer Institute University of Utah Salt Lake City UT United States Centre for Genomic a

Clinical genetic testing identifies variants causal for hereditary cancer, information that is used for risk assessment and clinical management. Unfortunately, some variants identified are of uncertain clinical significance (VUS), complicating patient management. Case-control data is one evidence type used to classify VUS. As an initiative of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Analytical Working Group we analyze germline sequencing data of BRCA1 and BRCA2 from 96,691 female breast cancer cases and 302,116 controls from three studies: the BRIDGES study of the Breast Cancer Association Consortium, the Cancer Risk Estimates Related to Susceptibility consortium, and the UK Biobank. We observe 11,207 BRCA1 and BRCA2 variants, with 6909 being coding, covering 23.4% of BRCA1 and BRCA2 VUS in ClinVar and 19.2% of ClinVar curated (likely) benign or pathogenic variants. Case-control likelihood ratio (ccLR) evidence is highly consistent with ClinVar assertions for (likely) benign or pathogenic variants;exhibiting 99.1% sensitivity and 95.3% specificity for BRCA1 and 93.3% sensitivity and 86.6% specificity for BRCA2. This approach provides case-control evidence for 787 unclassified variants;these include 579 with strong or moderate benign evidence and 10 with strong pathogenic evidence for which ccLR evidence is sufficient to alter clinical classification. © The Author(s) 2025.

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