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1. AER: Auto-Encoder with Regression for Time Series Anomaly Detection

Author

Wong, Lawrence, Liu, Dongyu, Berti-Equille, Laure, Alnegheimish, Sarah, and Veeramachaneni, Kalyan

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

Anomaly detection on time series data is increasingly common across various industrial domains that monitor metrics in order to prevent potential accidents and economic losses. However, a scarcity of labeled data and ambiguous definitions of anomalies can complicate these efforts. Recent unsupervised machine learning methods have made remarkable progress in tackling this problem using either single-timestamp predictions or time series reconstructions. While traditionally considered separately, these methods are not mutually exclusive and can offer complementary perspectives on anomaly detection. This paper first highlights the successes and limitations of prediction-based and reconstruction-based methods with visualized time series signals and anomaly scores. We then propose AER (Auto-encoder with Regression), a joint model that combines a vanilla auto-encoder and an LSTM regressor to incorporate the successes and address the limitations of each method. Our model can produce bi-directional predictions while simultaneously reconstructing the original time series by optimizing a joint objective function. Furthermore, we propose several ways of combining the prediction and reconstruction errors through a series of ablation studies. Finally, we compare the performance of the AER architecture against two prediction-based methods and three reconstruction-based methods on 12 well-known univariate time series datasets from NASA, Yahoo, Numenta, and UCR. The results show that AER has the highest averaged F1 score across all datasets (a 23.5% improvement compared to ARIMA) while retaining a runtime similar to its vanilla auto-encoder and regressor components. Our model is available in Orion, an open-source benchmarking tool for time series anomaly detection., Comment: This work is accepted by IEEE BigData 2022. The paper contains 10 pages, 6 figures, and 4 tables

Published
2022

2. Career and Life Planning Education: Extending the Self-Concept Theory and Its Multidimensional Model to Assess Career-Related Self-Concept of Students with Diverse Abilities

Author

Yang, Lan and Wong, Lawrence P. W.

Abstract

Purpose: This article aims to (1) systematically examine the development of career guidance practices in Hong Kong over the past 40 years, (2) discuss developmental attention to the career-related self-concept of diverse learners, and (3) propose a multidimensional model of self-concept by integrating the career-related domains with recent advances in self-concept research pertaining to students' in-school and post-school outcomes. Design/Approach/Methods: This article charts the developmental trend of career guidance and counseling (CGC) over more than 40 years in Hong Kong. The article also examines key findings relating to self-concept research made in the fields of education and career counseling in the past 50 years. Findings: For 50 years, Hong Kong has progressively recognized the importance of CGC. The government's continued determination to refine its policies and practices in this domain was succinctly highlighted in the Chief Executive's 2018 policy address. However, many challenges pertaining the professional competence of career guidance teachers and the ability of school administrators to manage the paradigm shift from informal to formal career guidance and counseling practices (CGCPs) remain. Meanwhile, the effects of these CGCPs on students' gains of career-related abilities and interests directly and indirectly remain under-researched. Originality/Value: This article integrates research into the developmental trend of career guidance practices in secondary schools and the study of academic self-concept. The article builds upon previous self-concept research by proposing an extended self-concept model that includes the career-related domain, setting a theoretical model for further research to explore. Finally, the article demonstrates the importance of tailoring career guidance activities in secondary education to reflect the diverse career-related self-concepts held by today's students with diverse abilities.

Published
2020
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3. Variants in ZFX are associated with an X-linked neurodevelopmental disorder with recurrent facial gestalt

Author

Shepherdson, James L., Hutchison, Katie, Don, Dilan Wellalage, McGillivray, George, Choi, Tae-Ik, Allan, Carolyn A., Amor, David J., Banka, Siddharth, Basel, Donald G., Buch, Laura D., Carere, Deanna Alexis, Carroll, Renée, Clayton-Smith, Jill, Crawford, Ali, Dunø, Morten, Faivre, Laurence, Gilfillan, Christopher P., Gold, Nina B., Gripp, Karen W., Hobson, Emma, Holtz, Alexander M., Innes, A. Micheil, Isidor, Bertrand, Jackson, Adam, Katsonis, Panagiotis, Amel Riazat Kesh, Leila, Küry, Sébastien, Lecoquierre, François, Lockhart, Paul, Maraval, Julien, Matsumoto, Naomichi, McCarrier, Julie, McCarthy, Josephine, Miyake, Noriko, Moey, Lip Hen, Németh, Andrea H., Østergaard, Elsebet, Patel, Rushina, Pope, Kate, Posey, Jennifer E., Schnur, Rhonda E., Shaw, Marie, Stolerman, Elliot, Taylor, Julie P., Wadman, Erin, Wakeling, Emma, White, Susan M., Wong, Lawrence C., Lupski, James R., Lichtarge, Olivier, Corbett, Mark A., Gecz, Jozef, Nicolet, Charles M., Farnham, Peggy J., Kim, Cheol-Hee, and Shinawi, Marwan

Published
2024
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4. Automated Process Incorporating Machine Learning Segmentation and Correlation of Oral Diseases with Systemic Health

Author

Yauney, Gregory, Rana, Aman, Wong, Lawrence C., Javia, Perikumar, Muftu, Ali, and Shah, Pratik

Subjects
Computer Science - Machine Learning, Quantitative Biology - Quantitative Methods, Statistics - Machine Learning
Abstract

Imaging fluorescent disease biomarkers in tissues and skin is a non-invasive method to screen for health conditions. We report an automated process that combines intraoral fluorescent porphyrin biomarker imaging, clinical examinations and machine learning for correlation of systemic health conditions with periodontal disease. 1215 intraoral fluorescent images, from 284 consenting adults aged 18-90, were analyzed using a machine learning classifier that can segment periodontal inflammation. The classifier achieved an AUC of 0.677 with precision and recall of 0.271 and 0.429, respectively, indicating a learned association between disease signatures in collected images. Periodontal diseases were more prevalent among males (p=0.0012) and older subjects (p=0.0224) in the screened population. Physicians independently examined the collected images, assigning localized modified gingival indices (MGIs). MGIs and periodontal disease were then cross-correlated with responses to a medical history questionnaire, blood pressure and body mass index measurements, and optic nerve, tympanic membrane, neurological, and cardiac rhythm imaging examinations. Gingivitis and early periodontal disease were associated with subjects diagnosed with optic nerve abnormalities (p <0.0001) in their retinal scans. We also report significant co-occurrences of periodontal disease in subjects reporting swollen joints (p=0.0422) and a family history of eye disease (p=0.0337). These results indicate cross-correlation of poor periodontal health with systemic health outcomes and stress the importance of oral health screenings at the primary care level. Our screening process and analysis method, using images and machine learning, can be generalized for automated diagnoses and systemic health screenings for other diseases., Comment: Submitted to IEEE Journal of Biomedical and Health Informatics, 2018

Published
2018

6. Frequency and Complexity of De Novo Structural Mutation in Autism

Author

Brandler, William M, Antaki, Danny, Gujral, Madhusudan, Noor, Amina, Rosanio, Gabriel, Chapman, Timothy R, Barrera, Daniel J, Lin, Guan Ning, Malhotra, Dheeraj, Watts, Amanda C, Wong, Lawrence C, Estabillo, Jasper A, Gadomski, Therese E, Hong, Oanh, Fajardo, Karin V Fuentes, Bhandari, Abhishek, Owen, Renius, Baughn, Michael, Yuan, Jeffrey, Solomon, Terry, Moyzis, Alexandra G, Maile, Michelle S, Sanders, Stephan J, Reiner, Gail E, Vaux, Keith K, Strom, Charles M, Zhang, Kang, Muotri, Alysson R, Akshoomoff, Natacha, Leal, Suzanne M, Pierce, Karen, Courchesne, Eric, Iakoucheva, Lilia M, Corsello, Christina, and Sebat, Jonathan

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Autism, Intellectual and Developmental Disabilities (IDD), Human Genome, Biotechnology, Mental Health, Pediatric, Brain Disorders, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Alleles, Amino Acid Sequence, Autism Spectrum Disorder, Base Sequence, Case-Control Studies, Child, DNA Copy Number Variations, Female, Gene Deletion, Gene Duplication, Gene Frequency, Gene Rearrangement, Genetic Loci, Genome, Human, Genotyping Techniques, Humans, INDEL Mutation, Male, Microarray Analysis, Molecular Sequence Data, Pedigree, Reproducibility of Results, Sensitivity and Specificity, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genetic studies of autism spectrum disorder (ASD) have established that de novo duplications and deletions contribute to risk. However, ascertainment of structural variants (SVs) has been restricted by the coarse resolution of current approaches. By applying a custom pipeline for SV discovery, genotyping, and de novo assembly to genome sequencing of 235 subjects (71 affected individuals, 26 healthy siblings, and their parents), we compiled an atlas of 29,719 SV loci (5,213/genome), comprising 11 different classes. We found a high diversity of de novo mutations, the majority of which were undetectable by previous methods. In addition, we observed complex mutation clusters where combinations of de novo SVs, nucleotide substitutions, and indels occurred as a single event. We estimate a high rate of structural mutation in humans (20%) and propose that genetic risk for ASD is attributable to an elevated frequency of gene-disrupting de novo SVs, but not an elevated rate of genome rearrangement.

Published
2016

7. Hemodynamic significance of intracranial atherosclerotic disease and ipsilateral imaging markers of cerebral small vessel disease

Author

Zheng, Lina, primary, Tian, Xuan, additional, Abrigo, Jill, additional, Fang, Hui, additional, Ip, Bonaventure YM, additional, Liu, Yuying, additional, Li, Shuang, additional, Liu, Yu, additional, Lan, Linfang, additional, Liu, Haipeng, additional, Ip, Hing Lung, additional, Fan, Florence SY, additional, Ma, Sze Ho, additional, Ma, Karen, additional, Lau, Alexander Y, additional, Soo, Yannie OY, additional, Leung, Howan, additional, Mok, Vincent CT, additional, Wong, Lawrence KS, additional, Xu, Yuming, additional, Liu, Liping, additional, Leng, Xinyi, additional, and Leung, Thomas W, additional

Published
2023
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8. Prepare, Do, Review: A Model Used to Reduce the Negative Feelings towards Laboratory Classes in an Introductory Chemistry Undergraduate Unit

Author

Spagnoli, Dino, Wong, Lawrence, Maisey, Shannan, and Clemons, Tristan D.

Abstract

Student feelings towards the laboratory component of an introductory chemistry unit were evaluated in an action research study, over a three-year period at the University of Western Australia. In 2013 we found that the percentage of students with negative feelings towards the laboratory increased over the duration of a semester. In 2014 we developed and introduced the use of pre-laboratory online activities, which the students found to be helpful in preparing them for the laboratory. However, there was no change in trend of negative feelings towards laboratory classes from 2013 to 2014. In 2015 we introduced the Prepare, Do, Review model and found that there was a reduction in the percentage of students with negative feelings towards laboratory classes compared with previous years. The Prepare, Do, Review model allows students more time to process the information given in the laboratory. We believe that this model could apply to laboratory programs in any discipline.

Published
2017
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10. Stroke: working toward a prioritized world agenda.

Author

Hachinski, Vladimir, Donnan, Geoffrey A, Gorelick, Philip B, Hacke, Werner, Cramer, Steven C, Kaste, Markku, Fisher, Marc, Brainin, Michael, Buchan, Alastair M, Lo, Eng H, Skolnick, Brett E, Furie, Karen L, Hankey, Graeme J, Kivipelto, Miia, Morris, John, Rothwell, Peter M, Sacco, Ralph L, Smith, Sidney C, Wang, Yulun, Bryer, Alan, Ford, Gary A, Iadecola, Costantino, Martins, Sheila CO, Saver, Jeff, Skvortsova, Veronika, Bayley, Mark, Bednar, Martin M, Duncan, Pamela, Enney, Lori, Finklestein, Seth, Jones, Theresa A, Kalra, Lalit, Kleim, Jeff, Nitkin, Ralph, Teasell, Robert, Weiller, Cornelius, Desai, Bhupat, Goldberg, Mark P, Heiss, Wolf-Dieter, Saarelma, Osmo, Schwamm, Lee H, Shinohara, Yukito, Trivedi, Bhargava, Wahlgren, Nils, Wong, Lawrence K, Hakim, Antoine, Norrving, Bo, Prudhomme, Stephen, Bornstein, Natan M, Davis, Stephen M, Goldstein, Larry B, Leys, Didier, and Tuomilehto, Jaakko

Subjects
Brain, Humans, Neurology, Public Health, Health Education, Recovery of Function, Technology, History, 20th Century, History, 21st Century, Internet, Guidelines as Topic, Stroke, Stroke Rehabilitation, Prevention, Rehabilitation, Aging, Brain Disorders, Clinical Research, Neurosciences, Quality Education, Good Health and Well Being, prevention, rehabilitation, stroke, translational, treatment, Clinical Sciences, Neurology & Neurosurgery
Abstract

Background and purposeThe aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke.MethodsPreliminary work was performed by seven working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium.ResultsRecommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent 'silo' mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (eg, social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries. Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. Educate and energize professionals, patients, the public and policy makers by using a 'Brain Health' concept that enables promotion of preventive measures.ConclusionsTo accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress.

Published
2010

13. Cilostazol Versus Aspirin in Ischemic Stroke Patients With High-Risk Cerebral Hemorrhage: Subgroup Analysis of the PICASSO Trial

Author

Kim, Bum Joon, Kwon, Sun U., Park, Joung-Ho, Kim, Yong-Jae, Hong, Keun-Sik, Wong, Lawrence K.S., Yu, Sungwook, Hwang, Yang-Ha, Lee, Ji Sung, Lee, Juneyoung, Rha, Jong-Ho, Heo, Sung Hyuk, Ahn, Seong Hwan, Seo, Woo-Keun, Park, Jong-Moo, Lee, Ju-Hun, Kwon, Jee-Hyun, Sohn, Sung-Il, Jung, Jin-Man, Navarro, Jose C., Kim, Hahn Young, Kim, Eung-Gyu, Kim, Seongheon, Cha, Jae-Kwan, Park, Man-Seok, Nam, Hyo Suk, and Kang, Dong-Wha

Published
2020
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16. The correlation between intracranial arterial calcification and the outcome of reperfusion therapy

Author

Du, Heng, Zheng, Jianrong, Li, Xuelong, Bos, Daniel, Yang, Wenjie, Cheng, Yajing, Liu, Cong, Wong, Lawrence Ka Sing, Hu, Jun, Chen, Xiangyan, Du, Heng, Zheng, Jianrong, Li, Xuelong, Bos, Daniel, Yang, Wenjie, Cheng, Yajing, Liu, Cong, Wong, Lawrence Ka Sing, Hu, Jun, and Chen, Xiangyan

Abstract

Objective: Intracranial arterial calcification (IAC) is a risk factor of ischemic stroke. However, the relationship between IAC patterns and clinical outcome of ischemic stroke remains controversial. We aimed to investigate the correlation between IAC patterns and the effects of reperfusion therapy among acute stroke patients. Methods: Consecutive acute ischemic stroke patients who underwent reperfusion therapy were included. IAC was categorized as intimal or medial. Based on its involvement, IAC was further classified as diffuse or focal. Neurologic dysfunction was assessed by the National Institute of Health stroke scale (NIHSS). Clinical outcome including favorable neurologic outcome (FNO) and early neurologic deterioration (END) were assessed. Results: Of 130 patients, 117 had IAC. Intimal IAC was identified in 74.6% of patients and medial IAC was present in 64.6% of patients. Diffuse IAC was present in 31.5% of patients. All diffuse IACs were medial pattern. Diffuse IAC was associated with higher baseline NIHSS (p = 0.011) and less FNO (p = 0.047). Compared with patients with focal or single diffuse IAC, patients with multiple diffuse IAC had higher baseline NIHSS (p = 0.002) and less FNO (p = 0.024). Multivariable linear regression (p < 0.001) and logistic regression (p = 0.027) suggested that multiple diffuse IAC was associated with higher baseline NIHSS and less FNO. No significant association was found between END and different IAC patterns. Interpretation: Multiple diffuse medial IAC may predict severer neurologic dysfunction and less favorable neurologic outcome after reperfusion therapy in acute stroke patients.

Published
2023

21. Intracranial Arterial Calcification and Intracranial Atherosclerosis:Close but Different

Author

Du, Heng, Li, Jia, Yang, Wenjie, Bos, Daniel, Zheng, Lu, Wong, Lawrence Ka Sing, Leung, Thomas W., Chen, Xiangyan, Du, Heng, Li, Jia, Yang, Wenjie, Bos, Daniel, Zheng, Lu, Wong, Lawrence Ka Sing, Leung, Thomas W., and Chen, Xiangyan

Abstract

Background and Purpose: Intracranial arterial calcification (IAC) may be present in the intimal or medial arterial layer. This study aimed to elucidate the link between the calcification and atherosclerotic disease in the intracranial vasculature. Methods: Consecutive patients with acute ischemic stroke were included. Bilateral intracranial segment of the internal carotid artery, M1 segment of the middle cerebral artery, intracranial segment of the vertebral artery, and the basilar artery were visualized by the multi-detector computed tomography (CT) and vessel-wall magnetic resonance imaging (vwMRI) within 14 days after stroke onset. IAC was into the intimal or medial pattern. Subsequently, on the vwMRI, we assessed the luminal stenosis, eccentricity, plaque burden, and intraplaque hemorrhage (IPH) as markers of atherosclerosis at each IAC site. Results: Among 69 patients with stroke, IAC was identified in 35% of (161/483) artery segments, of which 61.5% were predominantly intimal calcification and 38.5% were predominantly medial calcification. About 79.8% of intimal calcifications and 64.5% of medial calcifications co-existed with atherosclerotic plaques. Intimal calcification was associated with luminal stenosis (p = 0.003) caused by atherosclerotic lesions. Compared with the medial IAC, intimal IAC was more often accompanied by eccentric plaques (p = 0.02), larger plaque burden (p = 0.001), and IPH (p = 0.001). Conclusion: Our multimodal imaging-based comparison study on intracranial arteriosclerosis demonstrated that intimal IAC, compared with medial IAC, was more often accompanied by the luminal stenosis, larger plaque burden, eccentricity, and IPH, providing strong evidence for clinical evaluation on the mechanism, risk, and prognosis of ischemic stroke.

Published
2022

22. PNC-27, a Chimeric p53-Penetratin Peptide Binds to HDM-2 in a p53 Peptide-like Structure, Induces Selective Membrane-Pore Formation and Leads to Cancer Cell Lysis

Author

Sarafraz-Yazdi, Ehsan, Mumin, Stephen, Cheung, Diana, Fridman, Daniel, Lin, Brian, Wong, Lawrence, Rosal, Ramon, Rudolph, Rebecca, Frenkel, Matthew, Thadi, Anusha, Morano, William F., Bowne, Wilbur B., Pincus, Matthew R., Michl, Josef, Sarafraz-Yazdi, Ehsan, Mumin, Stephen, Cheung, Diana, Fridman, Daniel, Lin, Brian, Wong, Lawrence, Rosal, Ramon, Rudolph, Rebecca, Frenkel, Matthew, Thadi, Anusha, Morano, William F., Bowne, Wilbur B., Pincus, Matthew R., and Michl, Josef

Abstract

PNC-27, a 32-residue peptide that contains an HDM-2 binding domain and a cell-penetrating peptide (CPP) leader sequence kills cancer, but not normal, cells by binding to HDM-2 associated with the plasma membrane and induces the formation of pores causing tumor cell lysis and necrosis. Conformational energy calculations on the structure of PNC-27 bound to HDM-2 suggest that 1:1 complexes form between PNC-27 and HDM-2 with the leader sequence pointing away from the complex. Immuno-scanning electron microscopy was carried out with cancer cells treated with PNC-27 and decorated with an anti-PNC-27 antibody coupled to 6 nm gold particles and an anti-HDM-2 antibody linked to 15 nm gold particles. We found multiple 6 nm- and 15 nm-labeled gold particles in approximately 1:1 ratios in layered ring-shaped structures in the pores near the cell surface suggesting that these complexes are important to the pore structure. No pores formed in the control, PNC-27-treated untransformed fibroblasts. Based on the theoretical and immuno-EM studies, we propose that the pores are lined by PNC-27 bound to HDM-2 at the membrane surface with the PNC-27 leader sequence lining the pores or by PNC-27 bound to HDM-2.

Published
2022

23. Differences in Characteristics and Outcomes Between Asian and Non-Asian Patients in the TIAregistry.org

Author

Hoshino, Takao, Uchiyama, Shinichiro, Wong, Lawrence K.S., Sissani, Leila, Albers, Gregory W., Bornstein, Natan M., Caplan, Louis R., Donnan, Geoffrey A., Ferro, José M., Hennerici, Michael G., Labreuche, Julien, Lavallée, Philippa C., Molina, Carlos, Rothwell, Peter M., Steg, Philippe Gabriel, Touboul, Pierre-Jean, Vicaut, Éric, and Amarenco, Pierre

Published
2017
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24. Symptomatic Patients Remain at Substantial Risk of Arterial Disease Complications Before and After Endarterectomy or Stenting

Author

Hobeanu, Cristina, Lavallée, Philippa C., Rothwell, Peter M., Sissani, Leila, Albers, Gregory W., Bornstein, Natan M., Caplan, Louis R., Donnan, Geoffrey A., Ferro, José M., Hennerici, Michael G., Labreuche, Julien, Molina, Carlos, Steg, Philippe Gabriel, Touboul, Pierre-Jean, Uchiyama, Shinichiro, Vicaut, Éric, Wong, Lawrence K.S., and Amarenco, Pierre

Published
2017
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26. Loss-of-function variants in MYCBP2 cause neurobehavioural phenotypes and corpus callosum defects.

Author

AlAbdi, Lama, Desbois, Muriel, Rusnac, Domniţa-Valeria, Sulaiman, Raashda A, Rosenfeld, Jill A, Lalani, Seema, Murdock, David R, Burrage, Lindsay C, Network, Undiagnosed Diseases, Au, Ping Yee Billie, Towner, Shelley, Wilson, William G, Wong, Lawrence, Brunet, Theresa, Strobl-Wildemann, Gertrud, Burton, Jennifer E, Hoganson, George, McWalter, Kirsty, Begtrup, Amber, and Zarate, Yuri A

Subjects
CORPUS callosum, DYSGENESIS, GENOME editing, PHENOTYPES, AGENESIS of corpus callosum, CEREBRAL hemispheres, DEVELOPMENTAL delay, EPILEPSY
Abstract

The corpus callosum is a bundle of axon fibres that connects the two hemispheres of the brain. Neurodevelopmental disorders that feature dysgenesis of the corpus callosum as a core phenotype offer a valuable window into pathology derived from abnormal axon development. Here, we describe a cohort of eight patients with a neurodevelopmental disorder characterized by a range of deficits including corpus callosum abnormalities, developmental delay, intellectual disability, epilepsy and autistic features. Each patient harboured a distinct de novo variant in MYCBP2 , a gene encoding an atypical really interesting new gene (RING) ubiquitin ligase and signalling hub with evolutionarily conserved functions in axon development. We used CRISPR/Cas9 gene editing to introduce disease-associated variants into conserved residues in the Caenorhabditis elegans MYCBP2 orthologue, RPM-1, and evaluated functional outcomes in vivo. Consistent with variable phenotypes in patients with MYCBP2 variants, C. elegans carrying the corresponding human mutations in rpm-1 displayed axonal and behavioural abnormalities including altered habituation. Furthermore, abnormal axonal accumulation of the autophagy marker LGG-1/LC3 occurred in variants that affect RPM-1 ubiquitin ligase activity. Functional genetic outcomes from anatomical, cell biological and behavioural readouts indicate that MYCBP2 variants are likely to result in loss of function. Collectively, our results from multiple human patients and CRISPR gene editing with an in vivo animal model support a direct link between MYCBP2 and a human neurodevelopmental spectrum disorder that we term, MYCBP2 -related developmental delay with corpus callosum defects (MDCD). [ABSTRACT FROM AUTHOR]

Published
2023
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29. PNC-27, a Chimeric p53-Penetratin Peptide Binds to HDM-2 in a p53 Peptide-like Structure, Induces Selective Membrane-Pore Formation and Leads to Cancer Cell Lysis

Author

Sarafraz-Yazdi, Ehsan, primary, Mumin, Stephen, additional, Cheung, Diana, additional, Fridman, Daniel, additional, Lin, Brian, additional, Wong, Lawrence, additional, Rosal, Ramon, additional, Rudolph, Rebecca, additional, Frenkel, Matthew, additional, Thadi, Anusha, additional, Morano, William F., additional, Bowne, Wilbur B., additional, Pincus, Matthew R., additional, and Michl, Josef, additional

Published
2022
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31. Impact of Immune-Related Adverse Events on Efficacy of Immune Checkpoint Inhibitors in Patients with Advanced Hepatocellular Carcinoma

Author

Ng, Kennedy Yao Yi, primary, Tan, Sze Huey, additional, Tan, Jack Jie En, additional, Tay, Desiree Shu Hui, additional, Lee, Ailica Wan Xin, additional, Ang, Andrea Jing Shi, additional, Wong, Lawrence Wen Jun, additional, Choo, Su Pin, additional, Tai, David Wai-Meng, additional, and Lee, Joycelyn Jie Xin, additional

Published
2021
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34. Understanding the Clinical Implications of Intracranial Arterial Calcification Using Brain CT and Vessel Wall Imaging

Author

Yang, Wen-Jie, primary, Wasserman, Bruce A., additional, Zheng, Lu, additional, Huang, Zhong-Qing, additional, Li, Jia, additional, Abrigo, Jill, additional, Wong, Simon Sin-man, additional, Ying, Michael Tin-cheung, additional, Chu, Winnie Chiu-Wing, additional, Wong, Lawrence Ka-sing, additional, Leung, Thomas Wai-Hong, additional, and Chen, Xiang-Yan, additional

Published
2021
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35. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors

Author

Bakker, Mark K., van der Spek, Rick A.A., van Rheenen, Wouter, Morel, Sandrine, Bourcier, Romain, Hostettler, Isabel C., Alg, Varinder S., van Eijk, Kristel R., Koido, Masaru, Akiyama, Masato, Terao, Chikashi, Matsuda, Koichi, Walters, Robin G., Lin, Kuang, Li, Liming, Millwood, Iona Y., Chen, Zhengming, Rouleau, Guy A., Zhou, Sirui, Rannikmäe, Kristiina, Sudlow, Cathie L.M., Houlden, Henry, van den Berg, Leonard H., Dina, Christian, Naggara, Olivier, Gentric, Jean-Christophe, Shotar, Eimad, Eugène, François, Desal, Hubert, Winsvold, Bendik S., Børte, Sigrid, Johnsen, Marianne Bakke, Brumpton, Ben M., Sandvei, Marie Søfteland, Willer, Cristen J., Hveem, Kristian, Zwart, John-Anker, Verschuren, W. M. Monique, Friedrich, Christoph M., Hirsch, Sven, Schilling, Sabine, Dauvillier, Jérôme, Martin, Olivier, Martinsen, Amy E, Aamodt, Anne Hege, Skogholt, Anne Heidi, Sandset, Else Charlotte, Kristoffersen, Espen S, Ellekjaer, Hanne, Heuch, Ingrid, Nielsen, Jonas Bille, Hagen, Knut, Fritsche, Lars, Thomas, Laurent F., Pedersen, Linda, Gabrielsen, Maiken E, Vigeland, Maria Dehli, Holmen, Oddgeir, Zhou, Wei, Chen, Junshi, Chen (PI), Zhengming, Clarke, Robert, Collins, Rory, Guo, Yu, Li (PI), Liming, Liu, Depei, Lv, Jun, Peto, Richard, Walters, Robin, Avery, Daniel, Boxall, Ruth, Bennett, Derrick, Chang, Yumei, Chen, Yiping, Du, Huaidong, Gan, Wei, Gilbert, Simon, Hacker, Alex, Hill, Michael, Holmes, Michael, Iona, Andri, Kartsonaki, Christiana, Kerosi, Rene, Kong, Ling, Lancaster, Garry, Lewington, Sarah, McDonnell, John, Millwood, Iona, Nie, Qunhua, Ryder, Paul, Sansome, Sam, Schmidt-Valle, Dan, Sherliker, Paul, Sohoni, Rajani, Stevens, Becky, Turnbull, Iain, Wang, Lin, Wright, Neil, Yang, Ling, Yang, Xiaoming, Yao, Pang, Bian, Zheng, Han, Xiao, Hou, Can, Pei, Pei, Liu, Chao, Yu, Canqing, Pang, Zengchang, Gao, Ruqin, Li, Shanpeng, Wang, Shaojie, Liu, Yongmei, Du, Ranran, Cheng, Liang, Tian, Xiaocao, Zhang, Hua, Zhai, Yaoming, Ning, Feng, Sun, Xiaohui, Li, Feifei, Lv, Silu, Wang, Junzheng, Hou, Wei, Zou, Mingyuan, Yan, Shichun, Zhou, Xue, Yu, Bo, Li, Yanjie, Xu, Qinai, Kang, Quan, Guo, Ziyan, Wang, Dan, Hu, Ximin, Chen, Jinyan, Fu, Yan, Wang, Xiaohuan, Weng, Min, Guo, Zhendong, Wu, Shukuan, Li, Yilei, Li, Huimei, Wu, Ming, Zhou, Yonglin, Zhou, Jinyi, Tao, Ran, Yang, Jie, Su, Jian, liu, Fang, Zhang, Jun, Hu, Yihe, Lu, Yan, Ma, Liangcai, Tang, Aiyu, Hua, Yujie, Jin, Jianrong, Liu, Jingchao, Tang, Zhenzhu, Chen, Naying, Huang, Ying, Li, Mingqiang, Meng, Jinhuai, Pan, Rong, Jiang, Qilian, Lan, Jian, Liu, Yun, Wei, Liuping, Zhou, Liyuan, Chen, Ningyu, Wang, Ping, Meng, Fanwen, Qin Sisi Wang, Yulu, Wu, Xianping, Zhang, Ningmei, Chen, Xiaofang, Zhou, Weiwei, Luo, Guojin, Li, Jianguo, Zhong, Xunfu, Liu, Jiaqiu, Sun, Qiang, Ge, Pengfei, Ren, Xiaolan, Dong, Caixia, Zhang, Hui, Mao, Enke, Wang, Xiaoping, Wang, Tao, Zhang, Xi, Zhou, Ding Zhang, Zhou, Gang, Feng, Shixian, Chang, Ling, Fan, Lei, Gao, Yulian, He, Tianyou, Sun, Huarong, He, Pan, Hu, Chen, Zhang, Xukui, Wu, Huifang, Yu, Min, Hu, Ruying, Wang, Hao, Gong, Weiwei, Wang, Meng, Xie, Kaixu, Chen, Lingli, Pan, Dongxia, Gu, Qijun, Huang, Yuelong, Chen, Biyun, Yin, Li, Liu, Huilin, Fu, Zhongxi, Xu, Qiaohua, Xu, Xin, Zhang, Hao, Long, Huajun, Zhang, Libo, Nagai, Akiko, Muto, Kaori, Hirata, Makoto, Morisaki, Takayuki, Yamashita, Yasushi, Kamatani, Yoichiro, Kambara, Yoko, Murakami, Yoshinori, Masumoto, Akihide, Nagayama, Satoshi, Miki, Yoshio, Yoshimori, Kozo, Fujioka, Tomoaki, Takata, Ryo, Yamaji, Ken, Takahashi, Kazuhisa, Asai, Satoshi, Takahashi, Yasuo, Minami, Shiro, Yamaguchi, Hiroki, Koretsune, Yukihiro, Nishizawa, Yasuko, Kodama, Ken, Kutsumi, Hiromu, Suzuki, Takao, Sinozaki, Nobuaki, Murayama, Shigeo, Furukawa, Yoichi, Yamanashi, Yuji, Papagiannaki, Chrisanthi, Piotin, Michel, Trystram, Denis, Edjlali-Goujon, Myriam, Boulouis, Grégoire, Rodriguez, Christine, Hassen, Waghi Ben, Saleme, Suzanna, Mounayer, Charbel, Rouchaud, Aymeric, Levrier, Olivier, Aguettaz, Pierre, Combaz, Xavier, Pasco, Anne, l’Allinec, Vincent, Bintner, Marc, Molho, Marc, Pascale, Gauthier, Chivot, Cyril, Costalat, Vincent, Darganzil, Cyril, Bonafé, Alain, Januel, Anne Christine, Michelozzi, Caterina, Cognard, Christophe, Bonneville, Fabrice, Tall, Philippe, Darcourt, Jean, Biondi, Alessandra, Iosif, Cristina, Ferre, Jean Christophe, Gauvrit, Jean Yves, Eugene, François, Raoult, Hélène, Gentric, Jean Christophe, Ognard, Julien, Anxionnat, René, Gory, Benjamin, Bracard, Serge, Derelle, Anne Laure, Tonnelet, Romain, Spelle, Laurent, Ikka, Léon, Ozanne, Augustin, Gallas, Sophie, Caroff, Jildaz, Achour, Nidal Ben, Moret, Jacques, Chabert, Emmanuel, Berge, Jérôme, Marnat, Gaultier, Barreau, Xavier, Gariel, Florent, Clarencon, Frédéric, Aggour, Mohammed, Ricolfi, Frédéric, Chavent, Adrien, Thouant, Pierre, Lebidinsky, Pablo, Lemogne, Brivael, Herbreteau, Denis, Bibi, Richard, Janot, Kevin, Pierot, Laurent, Soize, Sébastien, Labeyrie, Marc Antoine, Vandendries, Christophe, Kazemi, Appoline, Leclerc, Xavier, Pruvo, Jean Pierre, Bricout, Nicolas, Velasco, Stéphane, Boucebci, Samy, Lemmens, Robin, Pandolfo, Massimo, Bodenant, Marie, Louillet, Fabien, Mas, Jean-Louis, Deltour, Sandrine, Leder, Sara, Léger, Anne, Canaple, Sandrine, Godefroy, Olivier, Giroud, Maurice, Jacquin, Agnès, Moulin, Thierry, Vuillier, Fabrice, Tzourio, Christophe, Santos, Michael Dos, Malik, Rainer, Hausser, Ingrid, Thomas-Feles, Constanze, Weber, Ralf, Grond-Ginsbach, Caspar, Hacke, Werner, Giossi, Alessia, Volonghi, Irene, Costa, Paolo, del Zotto, Elisabetta, Morotti, Andrea, Poli, Loris, Muiesan, Maria Lorenza, Salvetti, Massimo, Rosei, Enrico Agabiti, Lanfranconi, Silvia, Baron, Pierluigi, Ferrarese, Carlo, Susani, Emanuela, Giacalone, Giacomo, Paolucci, Stefano, Palmirotta, Raffaele, Guadagni, Fiorella, Paciaroni, Maurizio, Ballabio, Elena, Parati, Eugenio A., Fluri, Felix, Hatz, Florian, Gisler, Dominique, Amort, Margareth, Bevan, Steve, James, Tom, Olsson, Sandra, Holmegaard, Lukas, Altintas, Ayse, Martin, Juan José, Kittner, Steven, Mitchell, Braxton, Stine, Colin, O’Connell, Jeff, Dueker, Nicole, Koudstaal, Peter J., de Lau, Lonneke M.L., Hofman, Albert, Verhaaren, Benjamin F, Uitterlinden, Andre G, Montaner, Joan, Mendioroz, Maite, Yadav, Sunaina, Khan, Muhammad Saleem, Wilder, Michael, van Dijk, Ewoud, Maaijwee, Noortje, Rutten-Jacobs, Loes, Kramer, Jamie, Malik, Shaneela, Brott, Thomas G, Brown, Robert D, Singleton, Andrew, Hardy, John, Rich, Stephen S, Tanislav, Christian, Jungehülsing, Jan, Werring, David, Alg, Varinder, Hostettler, Isabel, Bonner, Stephen, Walsh, Daniel, Bulters, Diederik, Kitchen, Neil, Brown, Martin, Grieve, Joan, Roberts, Gareth, Jones, Timothy, Critchley, Giles, Sharma, Pankaj, Nelson, Richard, Whitfield, Peter, Ross, Stuart, Patel, Hiren, Eldridge, Paul, Saastamoinen, Kari, Patel, Umang, Lawrance, Enas, Vandabona, Subha, Mendelow, David, Teal, Rachel, Warner, Orlando, Kirkpatrick, Peter, Seshadri, Sudha, Kilarski, Laura, Hyacinth, Hyacinth I, Oliveira, Jamary, Marini, Sandro, Nyquist, Paul, Lewis, Cathryn, Norrving, Bo, Smith, Gustav, Rosand, Jonathan, Biffi, Alessandro, Kourkoulis, Christina, Anderson, Chris, Giese, Anne-Katrin, Bang, Oh Young, Chung, Jong-Won, Kim, Gyeong-Moon, Zhuang, Qishuai, Sheu, Wayne, Smalley, June, Howson, Joanna, Granata, Alessandra, Markus, Hugh, Wardlaw, Joanna, Cole, John, Thalamuthu, Anbupalam, Hopewell, Jemma, Worrall, Bradford, Bis, Josh, Tirschwell, David, Reiner, Alex, Dhar, Raj, Lee, Jin-Moo, Mortenson, Janne, Wassertheil-Smoller, Sylvia, Prasad, Kameshwar, Fisher, Mark, Traenka, Christopher, Wang, Xingwu, Wang, Yongjun, Rouanet, Francois, Sibon, Igor, Sarnowski, Chloé, Maillard, Pauline, Aparicio, Hugo Javier, Dupuis, Josee, Yang, Qiong, Luvizutto, Gustavo, Chasman, Daniel, Rexrode, Kathryn, Harriot, Andrea, Phuah, Chia-Ling, Santo, Gustavo, Gerard, Jen, Liu, Guiyou, Aaron, Sanjith, Christudass, Christhunesa S., Salomi, BSB, Sanghera, Dharambir, Boehme, Amelia, Elkind, Mitchell, Gretarsdottir, Solveig, Lange, Leslie, Rost, Natalia, James, Michael, Stewart, Jill, Goldstein, Larry, Waddy, Salina, Vojinovic, Dina, Ikram, Arfan, Thijs, Vincent, Parati, Eugenio, Boncoraglio, Giorgio, Kooperberg, Charles, Abboud, Sherrine, Zand, Ramin, Bijlenga, Philippe, Selim, Magdy, Happola, Olli, Strbian, Daniel, Tomppo, Liisa, Pathak, Abhishek, Pfeiffer, Dorothea, Aires, de Buenos, de Carvalho, Joao Jose Freitas, Ribeiro, Priscila, Torres, Nuria, Barboza, Miguel, Plomaritoglou, Androniki, Bjorkegren, Johan, Chan, Yu-Feng Yvonne, Gudnason, Villi, Jimenez-Conde, Jordi, Soriano, Carolina, Roquer, Jaume, Bentley, Paul, Tournier-Lasserve, Elisabeth, Dufouil, Carole, Debette, Stephanie, Mishra, Aniket, Wee, Lawrence, Siddiqi, Saima, Wu, Jer-Yuarn, Ko, Tai-Ming, Bione, Silvia, Jood, Katarina, Tatlisumak, Turgut, Arauz, Antonio, Korostynski, Michal, Launer, Lenore, Yue, Suo, bersano, anna, Juchniewicz, Karol Józef, Mateusz, Adamski, Pera, Joanna, Wnuk, Marcin, Levi, Christopher, Gusdon, Aaron, Kostulas, Konstantinos, Maxwell, Jessye, Duering, Marco, Jagiella, Jeremiasz, Hata, Jun, Ninomiya, Toshiharu, Nguyen, Vinh, Thorarinsson, Bjorn Logi, Lee, Tsong-Hai, Rakitko, Alexandr, Dichgans, Martin, Lindgren, Arne, Wasselius, Johan, Drake, Mattias, Stenman, Martin, Ilinca, Andreea, Staals, Julie, Sadr-Nabavi, Ariane, Crawford, Katherine, Lena, Umme, Mateen, Farrah, Ay, Hakan, Wu, Ona, Schirmer, Markus, Romero, Javier, Cramer, Steve, Golland, Polina, Mueller, Bertram, Brown, Robert, Meschia, James, Ross, Owen A., Pare, Guillaume, Chong, Mike, mansour, Ossama yassin, Karaszewski, Bartosz, Enzinger, Christian, Schmidt, Reinhold, Seiler, Stephan, Pichler, Alexander, Ovbiagele, Bruce, Yamada, Yoshiji, Rundek, Tatjana, Blanton, Susan, P, John, Chern, Joseph, O'Donnell, Chris, Corriveau, Roderick, Bhattacharya, Pallab, Gwinn, Katrina, CHANDRA, BHARATENDU, Chen, Christopher, Kalaria, Raj, Koenig, Jim, Singh, Om Prakash, Olugbodi, Akintomi, Giralt, Eva, Saleheen, Danish, de Leeuw, Frank-Erik, Klijn, Karin, Olesen, Jes, Kubo, Michiaki, Spence, David, Pedersen, Annie, Olsson, Maja, Martín, Juan José, Braga, Gabriel, Xu, Huichun, Assimes, Tim, Raskurazhev, Anton, Lee, Wei Ling, Burri, Philippe, Frid, Petrea, GmbH, Heilbronn, Deng, Zhen, Habibi-koolaee, Mahdi, Vijayan, Murali, Leung, Thomas, Wong, Lawrence, Mok, Vincent, Choy, Richard, Jern, Christina, Lebedeva, Elena, Farrall, Martin, Jiayuan, Xu, Loo, Keat Wei, Rinkel, Gabriel, Magnus, Rudolf, Goncalves, Anderson, Franca, Paulo, Cendes, Iscia, Carrera, Caty, Fernandez-Cadenas, Israel, Kim, Helen, Rolfs, Arndt, Owolabi, Mayowa, Bakker, Mark, Ruigrok, Ynte, Hauer, Allard, Pulit, Sara L., Algra, Ale, van der Laan, Sander W., Macleod, Mary, Howard, George, Tiwari, Hemant, Irvin, Ryan, Albright, Karen C., Perry, Rodney, Kidwell, Chelsea, Pavlovic, Aleksandra, Sargurupremraj, Murali, Schilling, Sabrina, Pezzini, Alessandro, Abd-Allah, Foad, DeCarli, Charles, Liebeskind, David, Traylor, Matthew, Tan, Rhea, Danesh, John, Larsson, Susanna C., Rutten, Loes, Donatti, Amanda, Avelar, Wagner, Broderick, Joseph, Woo, Daniel, Kissela, Brett, Ibenez, Laura Garcia, Salman, Rustam, Sudlow, Cathie, McDonough, Caitrin Wheeler, Silliman, Scott, Magvanjav, Oyunbileg, van Agtmael, Tom, Walters, Matthew, Lorentzen, Erik, Stanne, Tara, Olsson, Martina, Nakagawa, Kazuma, Akinyemi, Rufus, Cotlatciuc, Ioana, O'Connell, Jeff, Sparks, Mary, Sorkin, John, Dave, Tushar, Naylor, Jill, Brown, Devin, Du, Rose, Kulik, Tobias B., Attia, John, Faber, James E, Rothwell, Peter, Márquez, Elsa Valdés, Mancuso, Michelangelo, Souza, Doralina Brum, de Silva, Ranil, Vibo, Riina, Korv, Janika, Maguire, Jane, Fornage, Myriam, Illoh, Kachikwu, Milewicz, Dianna, Majersik, Jennifer, DeHavenon, Adam, Kalani, Yashar, Alexander, Matthew, Cushman, Mary, Sale, Michele, Owens, Debra, Keene, Keith, Rich, Stephe, Psaty, Bruce, Longstreth, Will, Atadzhanov, Masharip, Wolfe, Stacey Quintero, Langefeld, Carl, Bushnell, Cheryl, Cruchaga, Carlos, Konrad, Jan, Liu, Junfeng, Sheth, Kevin, Falcone, Guido, Donahue J, Kathleen, Jones, Gregory T., Bown, Matthew J., Ko, Nerissa U., Coleman, Jonathan R.I., Breen, Gerome, Zaroff, Jonathan G., Klijn, Catharina J.M., Sargurupremraj, Muralidharan, Amouyel, Philippe, Debette, Stéphanie, Rinkel, Gabriel J.E., Worrall, Bradford B., Slowik, Agnieszka, Gaál-Paavola, Emilia I., Niemelä, Mika, Jääskeläinen, Juha E., von Und Zu Fraunberg, Mikael, Lindgren, Antti, Broderick, Joseph P., Werring, David J., Redon, Richard, Veldink, Jan H., Ruigrok, Ynte M., Stroke, HUNT All-In, Group, China Kadoorie Biobank Collaborative, Consortium, BioBank Japan Project, Group, ICAN Study, Group, CADISP, investigators, Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study, (ISGC), International Stroke Genetics Consortium, Morel, Sandrine, and Bijlenga, Philippe Alexandre Pierre

Subjects
genetics [Blood Pressure], Medizin, Genome-wide association study, Blood Pressure, Disease, ddc:616.07, Bioinformatics, 616: Innere Medizin und Krankheiten, 0302 clinical medicine, Risk Factors, physiopathology [Hypertension], genetics [Genetic Predisposition to Disease], Genetic risk factor, Stroke, 0303 health sciences, Smoking, genetics [Smoking], genetics [Intracranial Aneurysm], Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Cerebrovascular disorder, 3. Good health, genetics [European Continental Ancestry Group], Hypertension, genetics [Polymorphism, Single Nucleotide], Subarachnoid hemorrhage, pathology [Intracranial Aneurysm], genetics [White People], Biology, Genetic correlation, pathology [Endothelial Cells], Polymorphism, Single Nucleotide, Article, White People, 03 medical and health sciences, Aneurysm, Asian People, ddc:570, Genetics, medicine, Humans, Genetic Predisposition to Disease, cardiovascular diseases, 030304 developmental biology, genetics [Subarachnoid Hemorrhage], genetics [Asian Continental Ancestry Group], 572: Biochemie, genetics [Asian People], pathology [Subarachnoid Hemorrhage], adverse effects [Smoking], Endothelial Cells, Subarachnoid Hemorrhage, medicine.disease, Intracranial aneurysm, Genetic architecture, ddc:616.8, Case-Control Studies, genetics [Hypertension], 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

An author correction to this article published in December 2020 is available at https://doi.org/10.1038/s41588-020-00760-4. Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.

Published
2021
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36. Retinal differential light sensitivity variation across the macula in healthy subjects : Importance of cone separation and loci eccentricity

Author

Sampson, Danuta M., Roshandel, Danial, Chew, Avenell L., Wang, Yufei, Stevenson, Paul G., Cooper, Matthew N., Ong, Elaine, Wong, Lawrence, La, Jonathan, Alonso-Caneiro, David, Chelva, Enid, Khan, Jane C., Sampson, David D., Chen, Fred K., Sampson, Danuta M., Roshandel, Danial, Chew, Avenell L., Wang, Yufei, Stevenson, Paul G., Cooper, Matthew N., Ong, Elaine, Wong, Lawrence, La, Jonathan, Alonso-Caneiro, David, Chelva, Enid, Khan, Jane C., Sampson, David D., and Chen, Fred K.

Abstract

Purpose: Microperimetry measures differential light sensitivity (DLS) at specific retinal locations. The aim of this study is to examine the variation in DLS across the macula and the contribution to this variation of cone distribution metrics and retinal eccentricity. Methods: Forty healthy eyes of 40 subjects were examined by microperimetry (MAIA) and adaptive optics imaging (rtx1). Retinal DLS was measured using the grid patterns: foveal (2°–3°), macular (3°–7°), and meridional (2°–8° on horizontal and vertical meridi-ans). Cone density (CD), distribution regularity, and intercone distance (ICD) were calcu-lated at the respective test loci coordinates. Linear mixed-effects regression was used to examine the association between cone distribution metrics and loci eccentricity, and retinal DLS. Results: An eccentricity-dependent reduction in DLS was observed on all MAIA grids, which was greatest at the foveal-parafoveal junction (2°–3°) (−0.58 dB per degree, 95% confidence interval [CI]; −0.91 to −0.24 dB, P < 0.01). Retinal DLS across the meridional grid changed significantly with each 1000 cells/deg2 change in CD (0.85 dB, 95% CI; 0.10 to 1.61 dB, P = 0.03), but not with each arcmin change in ICD (1.36 dB, 95% CI; −2.93 to 0.20 dB, P = 0.09). Conclusions: We demonstrate significant variation in DLS across the macula. Topographical change in cone separation is an important determinant of the variation in DLS at the foveal-parafoveal junction. We caution the extrapolation of changes in DLS measurements to cone distribution because the relationship between these variables is complex. Translational Relevance: Cone density is an independent determinant of DLS in the foveal-parafoveal junction in healthy eyes.

Published
2021

41. Retinal Differential Light Sensitivity Variation Across the Macula in Healthy Subjects: Importance of Cone Separation and Loci Eccentricity

Author

Sampson, Danuta M., primary, Roshandel, Danial, additional, Chew, Avenell L., additional, Wang, Yufei, additional, Stevenson, Paul G., additional, Cooper, Matthew N., additional, Ong, Elaine, additional, Wong, Lawrence, additional, La, Jonathan, additional, Alonso-Caneiro, David, additional, Chelva, Enid, additional, Khan, Jane C., additional, Sampson, David D., additional, and Chen, Fred K., additional

Published
2021
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43. A hybrid receiver scheme for multiuser multicode CDMA systems in multipath fading channels

Author

Thian, Boon Sim, Wang, Yuhong, Tjhung, Tjeng Thiang, and Wong, Lawrence Wai-Choong

Subjects
CDMA technology -- Research, Electromagnetic interference -- Control, Code Division Multiple Access technology, Business, Electronics, Electronics and electrical industries, Transportation industry
Abstract

In this paper, we present a system model for multiuser multicode code-division multiple access (CDMA) in a multipath fading channel and propose a hybrid receiver scheme for the system. Conventional receivers for CDMA systems utilized interference cancellation (IC) schemes, with the RAKE receiver as an initial data estimator. However, the RAKE receiver generates inaccurate data estimates due the interference that is caused by the cross correlation between the spreading codes. This inaccurate data estimate leads to significant error propagation to the subsequent stages and thus degrades the bit error rate (BER) performance. Our proposed scheme overcomes the problem by using a more accurate initial data estimator. It consists of an equalizer for obtaining initial data estimation, followed by several stages of parallel IC (PIC). Computer simulation results show that the BER curves of our proposed scheme do not encounter an error floor under all channel conditions; in contrast, the BER curves of the conventional RAKE-PIC receiver are constrained by an irreducible error floor. In addition, in an uplink four-path channel and at a BER of [10.sup.-3], our simulation results show that a one-stage PIC achieves a 2.5-dB gain over the first stage equalization receiver. Index Terms--Equalization, iterative interference cancellation (IC), multicode code-division multiple access (M-CDMA).

Published
2007

44. Two-dimensional halogen-bonded organic frameworks based on the tetrabromobenzene-1,4-dicarboxylic acid building molecule

Author

Chongboriboon, Nucharee, Samakun, Kodchakorn, Inprasit, Thitirat, Kielar, Filip, Dungkaew, Winya, Wong, Lawrence W.-Y., Sung, Herman H.-Y., Ninković, Dragan, Zarić, Snežana D., Chainok, Kittipong, Chongboriboon, Nucharee, Samakun, Kodchakorn, Inprasit, Thitirat, Kielar, Filip, Dungkaew, Winya, Wong, Lawrence W.-Y., Sung, Herman H.-Y., Ninković, Dragan, Zarić, Snežana D., and Chainok, Kittipong

Abstract

Two-dimensional (2D) halogen-bonded organic frameworks were readily engineered by strong and directional effects of the primary Br⋯O and the secondary Br⋯π halogen bonding interactions from the tetrabromobenzene-1,4-dicarboxylic acid (H2Br4BDC) building molecule involving 100% supramolecular yields. The 2D assembly can function as a host layered framework for the intercalation of various guest solvents including acetone (ATN), ethanol (EtOH), dimethyl sulfoxide (DMSO), and ethylene glycol (EG) resulting in a 1 : 2 host : guest complexation stoichiometry viz. H2Br4BDC·2S (S = ATN (1ATN), EtOH (2EtOH), DMSO (3DMSO), and EG (4EG)). All the solvates show remarkable similarities in their 2D layered sheets and the bilayer distance significantly responds to the size, shape, molecular conformation, and strength of the hydrogen bonding capability of the intercalated solvent molecules. The transition between solvate formation and desolvation was found to be facile and reversible upon the desolvation-resolvation process. The estimated Br⋯O halogen bonding energy of the solvates is in the -0.6 to -1.7 kcal mol-1 range, which was determined by quantum-mechanical calculations based on density functional theory (DFT) calculations. Furthermore, to quantitatively identify the host-guest intermolecular interactions of these solvates, they were visually compared by Hirshfeld surface analysis.

Published
2020

45. Supplementary data for article: Chongboriboon, N.; Samakun, K.; Inprasit, T.; Kielar, F.; Dungkaew, W.; Wong, L. W.-Y.; Sung, H. H.-Y.; Ninković, D. B.; Zarić, S. D.; Chainok, K. Two-Dimensional Halogen-Bonded Organic Frameworks Based on the Tetrabromobenzene-1,4-Dicarboxylic Acid Building Molecule. CrystEngComm 2019, 22 (1), 24–34. https://doi.org/10.1039/c9ce01140d

Author

Chongboriboon, Nucharee, Samakun, Kodchakorn, Inprasit, Thitirat, Kielar, Filip, Dungkaew, Winya, Wong, Lawrence W.-Y., Sung, Herman H.-Y., Ninković, Dragan, Zarić, Snežana D., Chainok, Kittipong, Chongboriboon, Nucharee, Samakun, Kodchakorn, Inprasit, Thitirat, Kielar, Filip, Dungkaew, Winya, Wong, Lawrence W.-Y., Sung, Herman H.-Y., Ninković, Dragan, Zarić, Snežana D., and Chainok, Kittipong

Published
2020

47. Dabigatran or Aspirin in East Asian Patients With Embolic Stroke of Undetermined Source: RE-SPECT ESUS Subgroup Analysis.

Author

Shinichiro Uchiyama, Kazunori Toyoda, Byung-Chul Lee, Chia-Wei Liou, Ka Sing Wong, Lawrence, Grauer, Claudia, Brueckmann, Martina, Atsushi Taniguchi, Yasuhisa Urano, Easton, J. Donald, Uchiyama, Shinichiro, Toyoda, Kazunori, Lee, Byung-Chul, Liou, Chia-Wei, Wong, Lawrence Ka Sing, Taniguchi, Atsushi, Urano, Yasuhisa, and RE-SPECT ESUS Investigators

Published
2021
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49. Grading Carotid Stenosis Using Ultrasonic Methods

Author

von Reutern, Gerhard-Michael, Goertler, Michael-Wolfgang, Bornstein, Natan M., Sette, Massimo Del, Evans, David H., Hetzel, Andreas, Kaps, Manfred, Perren, Fabienne, Razumovky, Alexander, Shiogai, Toshiyuki, Titianova, Ekaterina, Traubner, Pavel, Venketasubramanian, Narayanaswamy, Wong, Lawrence K.S., and Yasaka, Masahiro

Published
2012
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