90 results on '"Belgrave, D."'
Search Results
2. Evaluating Robustness to Dataset Shift via Parametric Robustness Sets
- Author
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Koyejo, S., Mohamed, S., Agarwal, A., Belgrave, D., Cho, K., Oh, A., Thams, Nikolaj, Oberst, Michael, Sontag, David, Koyejo, S., Mohamed, S., Agarwal, A., Belgrave, D., Cho, K., Oh, A., Thams, Nikolaj, Oberst, Michael, and Sontag, David
- Abstract
We give a method for proactively identifying small, plausible shifts in distribution which lead to large differences in model performance. These shifts are defined via parametric changes in the causal mechanisms of observed variables, where constraints on parameters yield a “robustness set” of plausible distributions and a corresponding worst-case loss over the set. While the loss under an individual parametric shift can be estimated via reweighting techniques such as importance sampling, the resulting worst-case optimization problem is non-convex, and the estimate may suffer from large variance. For small shifts, however, we can construct a local second-order approximation to the loss under shift and cast the problem of finding a worst-case shift as a particular non-convex quadratic optimization problem, for which efficient algorithms are available. We demonstrate that this second-order approximation can be estimated directly for shifts in conditional exponential family models, and we bound the approximation error. We apply our approach to a computer vision task (classifying gender from images), revealing sensitivity to shifts in non-causal attributes.
- Published
- 2022
3. Understanding Aesthetics with Language: A Photo Critique Dataset for Aesthetic Assessment
- Author
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Koyejo, S, Mohamed, S, Agarwal, A, Belgrave, D, Cho, K, Oh, A, Vera Nieto, D, Celona, L, Fernandez-Labrador, C, Koyejo, S, Mohamed, S, Agarwal, A, Belgrave, D, Cho, K, Oh, A, Vera Nieto, D, Celona, L, and Fernandez-Labrador, C
- Abstract
Computational inference of aesthetics is an ill-defined task due to its subjective nature. Many datasets have been proposed to tackle the problem by providing pairs of images and aesthetic scores based on human ratings. However, humans are better at expressing their opinion, taste, and emotions by means of language rather than summarizing them in a single number. In fact, photo critiques provide much richer information as they reveal how and why users rate the aesthetics of visual stimuli. In this regard, we propose the Reddit Photo Critique Dataset (RPCD), which contains tuples of image and photo critiques. RPCD consists of 74K images and 220K comments and is collected from a Reddit community used by hobbyists and professional photographers to improve their photography skills by leveraging constructive community feedback. The proposed dataset differs from previous aesthetics datasets mainly in three aspects, namely (i) the large scale of the dataset and the extension of the comments criticizing different aspects of the image, (ii) it contains mostly UltraHD images, and (iii) it can easily be extended to new data as it is collected through an automatic pipeline. To the best of our knowledge, in this work, we propose the first attempt to estimate the aesthetic quality of visual stimuli from the critiques. To this end, we exploit the polarity of the sentiment of criticism as an indicator of aesthetic judgment. We demonstrate how sentiment polarity correlates positively with the aesthetic judgment available for two aesthetic assessment benchmarks. Finally, we experiment with several models by using the sentiment scores as a target for ranking images. Dataset and baselines are available.
- Published
- 2022
4. Polynomial Neural Fields for Subband Decomposition and Manipulation
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Koyejo, S., Mohamed, S., Agarwal, A., Belgrave, D., Cho, K., Oh, A., Yang, Guandao, Benaim, Sagie, Jampani, Varun, Genova, Kyle, Barron, Jonathan T., Funkhouser, Thomas, Hariharan, Bharath, Belongie, Serge, Koyejo, S., Mohamed, S., Agarwal, A., Belgrave, D., Cho, K., Oh, A., Yang, Guandao, Benaim, Sagie, Jampani, Varun, Genova, Kyle, Barron, Jonathan T., Funkhouser, Thomas, Hariharan, Bharath, and Belongie, Serge
- Abstract
Neural fields have emerged as a new paradigm for representing signals, thanks to their ability to do it compactly while being easy to optimize. In most applications, however, neural fields are treated like black boxes, which precludes many signal manipulation tasks. In this paper, we propose a new class of neural fields called polynomial neural fields (PNFs). The key advantage of a PNF is that it can represent a signal as a composition of a number of manipulable and interpretable components without losing the merits of neural fields representation. We develop a general theoretical framework to analyze and design PNFs. We use this framework to design Fourier PNFs, which match state-of-the-art performance in signal representation tasks that use neural fields. In addition, we empirically demonstrate that Fourier PNFs enable signal manipulation applications such as texture transfer and scale-space interpolation. Code is available at https://github.com/stevenygd/PNF.
- Published
- 2022
5. Fair and Optimal Decision Trees: A Dynamic Programming Approach
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van der Linden, J.G.M., de Weerdt, M.M., Demirović, E., Koyejo, S., Mohamed, S., Agarwal, A., Belgrave, D., Cho, K., and Oh, A.
- Subjects
dynamic programming ,optimal decision trees ,fairness - Abstract
Interpretable and fair machine learning models are required for many applications, such as credit assessment and in criminal justice. Decision trees offer this interpretability, especially when they are small. Optimal decision trees are of particular interest because they offer the best performance possible for a given size. However, state-of-the-art algorithms for fair and optimal decision trees have scalability issues, often requiring several hours to find such trees even for small datasets. Previous research has shown that dynamic programming (DP) performs well for optimizing decision trees because it can exploit the tree structure. However, adding a global fairness constraint to a DP approach is not straightforward, because the global constraint violates the condition that subproblems should be independent. We show how such a constraint can be incorporated by introducing upper and lower bounds on final fairness values for partial solutions of subproblems, which enables early comparison and pruning. Our results show that our model can find fair and optimal trees several orders of magnitude faster than previous methods, and now also for larger datasets that were previously beyond reach. Moreover, we show that with this substantial improvement our method can find the full Pareto front in the trade-off between accuracy and fairness.
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- 2022
6. Polymorphisms of endotoxin pathway and endotoxin exposure: in vitro IgE synthesis and replication in a birth cohort
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Sahiner, U. M., Semic-Jusufagic, A., Curtin, J. A., Birben, E., Belgrave, D., Sackesen, C., Simpson, A., Yavuz, T. S., Akdis, C. A., Custovic, A., and Kalayci, O.
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- 2014
- Full Text
- View/download PDF
7. Impact of rhinitis on asthma severity in school-age children
- Author
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Deliu, M., Belgrave, D., Simpson, A., Murray, C. S., Kerry, G., and Custovic, A.
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- 2014
- Full Text
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8. G89 Individual Risk Assessment Tool for Asthma Prediction at School Age in a UK Birth Cohort
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Wang, R, Custovic, A, Simpson, A, Belgrave, D, and Murray, CS
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- 2014
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9. An international collaborative study to investigate a proposed reference method for the determination of potency measurements of fibrinolytics in absolute units
- Author
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LONGSTAFF, C., WHITTON, C., THELWELL, C., and BELGRAVE, D.
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- 2007
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10. Multiple atopy phenotypes and their associations with asthma: similar findings from two birth cohorts
- Author
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Lazic, N., Roberts, G., Custovic, A., Belgrave, D., Bishop, C. M., Winn, J., Curtin, J. A., Hasan Arshad, S., Simpson, A., and Weidinger, Stephan
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- 2013
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11. Methylation of IL-2 promoter at birth alters the risk of asthma exacerbations during childhood
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Curtin, J. A., Simpson, A., Belgrave, D., Semic-Jusufagic, A., Custovic, A., and Martinez, F. D.
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- 2013
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12. Patterns of paracetamol use in early life as a marker of susceptibility to asthma: 132
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Belgrave, D, Semic-Jusufagic, A, Simpson, A, Pickles, A, and Custovic, A
- Published
- 2010
13. Features of asthma which provide meaningful insights for understanding the disease heterogeneity
- Author
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Deliu, M., Yavuz, T. S., Sperrin, M., Belgrave, D., Sahiner, U. M., Sackesen, C., Kalayci, O., Custovic, A., MRC Health eResearch Centre (HeRC), and Çocuk Sağlığı ve Hastalıkları
- Subjects
severe asthma ,Male ,Severe asthma ,Allergy ,Adolescent ,allergic sensitization ,Severity of Illness Index ,Cluster analysis ,Humans ,Child ,Allergic sensitization ,childhood ,phenotypes ,Models, Immunological ,asthma ,Childhood ,Asthma ,respiratory tract diseases ,1117 Public Health And Health Services ,1107 Immunology ,endotypes ,Original Article ,Female ,ORIGINAL ARTICLES ,Epidemiology of Allergic Disease ,cluster analysis - Abstract
Background: Data-driven methods such as hierarchical clustering (HC) and principal component analysis (PCA) have been used to identify asthma subtypes, with inconsistent results. Objective: To develop a framework for the discovery of stable and clinically meaningful asthma subtypes. Methods: We performed HC in a rich dataset from 613 asthmatic children, using 45 clinical variables (Model 1), and after PCA dimensionality reduction (Model 2). Clinical experts then identified a set of asthma features/domains which informed clusters in the two analyses. In Model 3, we re-clustered the data using these features to ascertain whether this improved the discovery process.Results: Cluster stability was poor in Models 1 and 2. Clinical experts highlighted four asthma features/domains which differentiated the clusters in two models: age of onset, allergic sensitization, severity, and recent exacerbations. In Model 3 (HC using these four features), cluster stability improved substantially. The cluster assignment changed, providing more clinically interpretable results. In a 5-cluster model, we labelled the clusters as: “Difficult asthma” (n=132); “Early-onset mild atopic” (n=210); “Early-onset mild non-atopic: (n=153); “Late-onset” (n=105); and “Exacerbation-prone asthma” (n=13). Multinomial regression demonstrated that lung function was significantly diminished among children with “Difficult asthma”; blood eosinophilia was a significant feature of “Difficult”, “Early-onset mild atopic”, and “Late-onset asthma”. Children with moderate-severe asthma were present in each cluster.Conclusions and clinical relevance: An integrative approach of blending the data with clinical expert domain knowledge identified four features, which may be informative for ascertaining asthma endotypes. These findings suggests that variables which are key determinants of asthma presence, severity or control, may not be the most informative for determining asthma subtypes. Our results indicate that exacerbation-prone asthma may be a separate asthma endotype, and that severe asthma is not a single entity, but an extreme end of the spectrum of several different asthma endotypes.
- Published
- 2017
14. Evolution of IgE responses to multiple allergen components throughout childhood
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Howard, R, Belgrave, D, Papastamoulis, P, Simpson, A, Rattray, M, Custovic, A, and Medical Research Council (MRC)
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Male ,Allergy ,MCMC, Markov chain Monte Carlo algorithm ,Adolescent ,Immunology ,CHAIN MONTE-CARLO ,CHILDREN ,Article ,component-resolved diagnostics ,rhinitis ,Machine learning ,Humans ,R PACKAGE ,HDM, House dust mite ,Child ,CRD, Component-resolved diagnostics ,childhood ,Science & Technology ,BIRTH COHORT ,Infant ,SPT, Skin prick test ,Bayes Theorem ,Immunoglobulin E ,Allergens ,asthma ,PREDICTIVE-VALUE ,PR, Pathogenesis-related ,CLINICAL SYMPTOMS ,machine learning ,MANCHESTER ASTHMA ,1107 Immunology ,ATOPY ,Child, Preschool ,RISK-FACTORS ,LABEL SWITCHING PROBLEM ,IgE ,ISAC, Immuno Solid-phase Allergen Chip ,Life Sciences & Biomedicine ,OR, Odds ratio - Abstract
Background There is a paucity of information about longitudinal patterns of IgE responses to allergenic proteins (components) from multiple sources. Objectives This study sought to investigate temporal patterns of component-specific IgE responses from infancy to adolescence, and their relationship with allergic diseases. Methods In a population-based birth cohort, we measured IgE to 112 components at 6 follow-ups during childhood. We used a Bayesian method to discover cross-sectional sensitization patterns and their longitudinal trajectories, and we related these patterns to asthma and rhinitis in adolescence. Results We identified 1 sensitization cluster at age 1, 3 at age 3, 4 at ages 5 and 8, 5 at age 11, and 6 at age 16 years. “Broad” cluster was the only cluster present at every follow-up, comprising components from multiple sources. “Dust mite” cluster formed at age 3 years and remained unchanged to adolescence. At age 3 years, a single-component “Grass” cluster emerged, which at age 5 years absorbed additional grass components and Fel d 1 to form the “Grass/cat” cluster. Two new clusters formed at age 11 years: “Cat” cluster and “PR-10/profilin” (which divided at age 16 years into “PR-10” and “Profilin”). The strongest contemporaneous associate of asthma at age 16 years was sensitization to dust mite cluster (odds ratio: 2.6; 95% CI: 1.2-6.1; P
- Published
- 2018
15. Disaggregating Asthma:Big Investigation vs. Big Data
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Belgrave, D, Henderson, J, Simpson, A, Buchan, I, Bishop, C, Custovic, A, and Medical Research Council (MRC)
- Subjects
Big Data ,Machine Learning ,birth cohorts ,machine learning ,Allergy ,1107 Immunology ,endotypes ,big data ,Statistics ,Asthma - Abstract
We are facing a major challenge in bridging the gap between identifying subtypes of asthma, to understanding causal mechanisms, and translating this knowledge into personalized prevention and management strategies. In recent years, "big data" has been sold as a panacea for generating hypotheses and driving new frontiers of healthcare; the idea that the data must and will speak for themselves is fast becoming a new dogma. One of the dangers of ready accessibility of healthcare data and computational tools for data analysis is that the process of data mining may become uncoupled from the scientific process of clinical interpretation, understanding the provenance of the data and external validation. Although advances in computational methods can be valuable for using unexpected structure in data to generate hypotheses, there remains a need for testing hypotheses and interpreting results with scientific rigor. We argue for combining data-driven and hypothesis-driven methods in a careful synergy, and the importance of carefully characterized birth and patient cohorts with genetic, phenotypic, biological and molecular data in this process cannot be overemphasized. The main challenge on the road ahead is to harness 'bigger' healthcare data in ways that produce meaningful clinical interpretation and to translate this into better diagnoses and properly personalized prevention and treatment plans. There is a pressing need for cross-disciplinary research with an integrative approach to data science, whereby basic scientists, clinicians, data analysts and epidemiologists work together to understand the heterogeneity of asthma.
- Published
- 2017
16. Features of asthma which provide meaningful insights for understanding the disease heterogeneity
- Author
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Saçkesen, Cansın (ORCID 0000-0002-1115-9805 & YÖK ID 182537), Deliu, M.; Yavuz, T.S.; Sperrin, M.; Belgrave, D.; Sahiner, U.M.; Sackesen, C.; Kalayci, O.; Custovic, A., School of Medicine, Department of Pediatric Allergy, Saçkesen, Cansın (ORCID 0000-0002-1115-9805 & YÖK ID 182537), Deliu, M.; Yavuz, T.S.; Sperrin, M.; Belgrave, D.; Sahiner, U.M.; Sackesen, C.; Kalayci, O.; Custovic, A., School of Medicine, and Department of Pediatric Allergy
- Abstract
Background: Data-driven methods such as hierarchical clustering (HC) and principal component analysis (PCA) have been used to identify asthma subtypes, with inconsistent results. ObjectiveTo develop a framework for the discovery of stable and clinically meaningful asthma subtypes. MethodsWe performed HC in a rich data set from 613 asthmatic children, using 45 clinical variables (Model 1), and after PCA dimensionality reduction (Model 2). Clinical experts then identified a set of asthma features/domains which informed clusters in the two analyses. In Model 3, we reclustered the data using these features to ascertain whether this improved the discovery process. ResultsCluster stability was poor in Models 1 and 2. Clinical experts highlighted four asthma features/domains which differentiated the clusters in two models: age of onset, allergic sensitization, severity, and recent exacerbations. In Model 3 (HC using these four features), cluster stability improved substantially. The cluster assignment changed, providing more clinically interpretable results. In a 5-cluster model, we labelled the clusters as: Difficult asthma (n=132); Early-onset mild atopic (n=210); Early-onset mild non-atopic: (n=153); Late-onset (n=105); and Exacerbation-prone asthma (n=13). Multinomial regression demonstrated that lung function was significantly diminished among children with Difficult asthma; blood eosinophilia was a significant feature of Difficult, Early-onset mild atopic, and Late-onset asthma. Children with moderate-to-severe asthma were present in each cluster. Conclusions and clinical relevanceAn integrative approach of blending the data with clinical expert domain knowledge identified four features, which may be informative for ascertaining asthma endotypes. These findings suggest that variables which are key determinants of asthma presence, severity, or control may not be the most informative for determining asthma subtypes. Our results indicate that exacerbation-prone asthma m, MRC Health eResearch Centre (HeRC) grant; MRC
- Published
- 2017
17. Allergen-specific biomarkers to distinguish severe asthma endotypes
- Author
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Belgrave, D, Simpson, A, Custovic, A, and Medical Research Council (MRC)
- Subjects
Science & Technology ,Allergy ,1107 Immunology ,Immunology ,Life Sciences & Biomedicine - Published
- 2016
18. Phenotyping immune responses In asthma and respiratory infections
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Lin, L, Belgrave, D, Bakhsoliani, E, Hirsman, A, Edwards, MR, Walton, RP, Solari, R, Curtin, JA, Simpson, A, Rattray, M, Custovic, A, Johnston, SL, J P Moulton Charitable Foundation, Medical Research Council (MRC), and Medical Research Council
- Subjects
Science & Technology ,Critical Care Medicine ,General & Internal Medicine ,Respiratory System ,11 Medical And Health Sciences ,Life Sciences & Biomedicine - Published
- 2016
19. P120 Challenges in using hierarchical clustering to identify asthma subtypes: choosing the variables and variable transformation
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Deliu, M, primary, Yavuz, S, additional, Sperrin, M, additional, Belgrave, D, additional, Sackesen, C, additional, Sahiner, U, additional, Custovic, A, additional, and Kalayci, O, additional
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- 2016
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20. Distinguishing benign from pathologic TH2 immunity in atopic children
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Holt, PG, Strickland, D, Bosco, A, Belgrave, D, Hales, B, Simpson, A, Hollams, E, Holt, B, Kusel, M, Ahlstedt, S, Sly, Peter, Custovic, A, Holt, PG, Strickland, D, Bosco, A, Belgrave, D, Hales, B, Simpson, A, Hollams, E, Holt, B, Kusel, M, Ahlstedt, S, Sly, Peter, and Custovic, A
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- 2016
21. P46 The Influence Of Age And Gender On Allergy Test Results: Implications For The Use As Biomarkers In Childhood Asthma
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Mohammad, H., primary, Belgrave, D., additional, Harding, K., additional, Simpson, A., additional, and Custovic, A., additional
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- 2014
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22. Polymorphisms of endotoxin pathway and endotoxin exposure:in vitroIgE synthesis and replication in a birth cohort
- Author
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Sahiner, U. M., primary, Semic-Jusufagic, A., additional, Curtin, J. A., additional, Birben, E., additional, Belgrave, D., additional, Sackesen, C., additional, Simpson, A., additional, Yavuz, T. S., additional, Akdis, C. A., additional, Custovic, A., additional, and Kalayci, O., additional
- Published
- 2014
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23. Risk-Driven Design of Perception Systems
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Corso, Anthony L., Katz, Sydney M., Innes, Craig, Du, Xin, Ramamoorthy, Subramanian, Kochenderfer, Mykel J., Koyejo, S., Mohamed, S., Agarwal, A., Belgrave, D., Cho, K., and Oh, A.
- Abstract
Modern autonomous systems rely on perception modules to process complex sensor measurements into state estimates. These estimates are then passed to a controller, which uses them to make safety-critical decisions. It is therefore important that we design perception systems to minimize errors that reduce the overall safety of the system. We develop a risk-driven approach to designing perception systems that accounts for the effect of perceptual errors on the performance of the fully-integrated, closed-loop system. We formulate a risk function to quantify the effect of a given perceptual error on overall safety, and show how we can use it to design safer perception systems by including a risk-dependent term in the loss function and generating training data in risk-sensitive regions. We evaluate our techniques on a realistic vision-based aircraft detect and avoid application and show that risk-driven design reduces collision risk by 37% over a baseline system.
- Published
- 2023
24. Distilling Representations from GAN Generator via Squeeze and Span
- Author
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Yang, Yu, Cheng, Xiaotian, Liu, Chang, Bilen, Hakan, Ji, Xiangyang, Koyejo, S., Mohamed, S., Agarwal, A., Belgrave, D., Cho, K., and Oh, A.
- Abstract
In recent years, generative adversarial networks (GANs) have been an actively studied topic and shown to successfully produce high-quality realistic images in various domains. The controllable synthesis ability of GAN generators suggests that they maintain informative, disentangled, and explainable image representations, but leveraging and transferring their representations to downstream tasks is largely unexplored. In this paper, we propose to distill knowledge from GAN generators by squeezing and spanning their representations. We squeeze the generator features into representations that are invariant to semantic-preserving transformations through a network before they are distilled into the student network. We span the distilled representation of the synthetic domain to the real domain by also using real training data to remedy the mode collapse of GANs and boost the student network performance in a real domain. Experiments justify the efficacy of our method and reveal its great significance in self-supervised representation learning. Code will be made public.
- Published
- 2023
25. Don’t Roll the Dice, Ask Twice: The Two-Query Distortion of Matching Problems and Beyond
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Amanatidis, Georgios, Birmpas, Georgios, Filos-Ratsikas, Aris, Voudouris, Alexandros A., Koyejo, S., Mohamed, S., Agarwal, A., Belgrave, D., Cho, K., and Oh, A.
- Abstract
In most social choice settings, the participating agents express their preferencesover the different alternatives in the form of linear orderings. While this clearlysimplifies preference elicitation, it inevitably leads to poor performance with respect to optimizing a cardinal objective, such as the social welfare, since the values of the agents remain virtually unknown. This loss in performance because of lack of information is measured by the notion of distortion. A recent array of works put forward the agenda of designing mechanisms that learn the values of the agents for a small number of alternatives via queries, and use this limited extra information to make better-informed decisions, thus improving distortion. Following this agenda, in this work we focus on a class of combinatorial problems that includes most well-known matching problems and several of their generalizations, such as One-Sided Matching, Two-Sided Matching, General Graph Matching, and κ- Constrained Resource Allocation. We design two-query mechanisms that achieve the best-possible worst-case distortion in terms of social welfare, and outperform the best-possible expected distortion achieved by randomized ordinal mechanisms.
- Published
- 2023
26. Causal inference methods for supporting, understanding, and improving decision-making
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Bica, I, Belgrave, D, Noble, A, van der Schaar, M, and Prisacariu, V
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Machine learning - Abstract
Causality and the ability to reason about cause-and-effect relationships are central to decision-making. This thesis contributes to the area of causal inference by proposing new machine learning methods that can be used for supporting, understanding, and improving decision-making, with a focus on the healthcare setting. Firstly, we introduce several causal inference tools for supporting decision-making by estimating the causal effects of interventions (treatments) from observational data, such as electronic health records. We begin by addressing the under-explored problem of estimating counterfactual outcomes for continuous-valued interventions and propose a method based on generative adversarial networks that achieves state-of-the-art performance and that can help us choose both the correct treatment and dosage for each patient. Then, we shift our attention to the temporal setting where we develop a sequence-to-sequence model that uses domain adversarial training to handle time-dependent confounding and that can help us determine the best sequence of treatments for each patient. Moreover, we introduce the first method that can handle the presence of multi-cause hidden confounders in temporal data. By taking advantage of the dependencies in the treatment assignments over time, our method learns latent variables that can be used as substitutes for the hidden confounders. Secondly, we integrate counterfactual reasoning into batch inverse reinforcement learning to develop a method for better understanding the decision-making behaviour of experts by modelling their reward functions in terms of preferences over `what-if' (counterfactual) outcomes. We show that this allows us to obtain an interpretable parameterization of the experts' decision-making process and subsequently uncover the trade-offs and preferences associated with their actions. Thirdly, we improve the robustness of decision-making by proposing a new model for batch imitation learning that incorporates causal structure into the learnt imitation policy. By ensuring that the imitation policy only depends on the causal parents of the actions, we learn a decision-making guideline that is robust to spurious correlations and that generalizes well to new environments. Overall, this thesis introduces methodological advances in machine learning capable of reasoning about cause-and-effect relationships that can enable us to improve delivery of personalized care for patients, support clinical decision-making and build a more transparent account of clinical practice. We provide a discussion highlighting the challenges of incorporating such methods into practice and include suggestions for future work in this direction.
- Published
- 2023
27. TempEL: Linking Dynamically Evolving and Newly Emerging Entities
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Zaporojets, Klim, Kaffee, Lucie-Aimee, Deleu, Johannes, Demeester, Thomas, Develder, Chris, Augenstein, Isabelle, Koyejo, S., Mohamed, S., Agarwal, A., Belgrave, D., Cho, K., and Oh, A.
- Subjects
FOS: Computer and information sciences ,Computer Science - Computation and Language ,Technology and Engineering ,Computation and Language (cs.CL) - Abstract
In our continuously evolving world, entities change over time and new, previously non-existing or unknown, entities appear. We study how this evolutionary scenario impacts the performance on a well established entity linking (EL) task. For that study, we introduce TempEL, an entity linking dataset that consists of time-stratified English Wikipedia snapshots from 2013 to 2022, from which we collect both anchor mentions of entities, and these target entities' descriptions. By capturing such temporal aspects, our newly introduced TempEL resource contrasts with currently existing entity linking datasets, which are composed of fixed mentions linked to a single static version of a target Knowledge Base (e.g., Wikipedia 2010 for CoNLL-AIDA). Indeed, for each of our collected temporal snapshots, TempEL contains links to entities that are continual, i.e., occur in all of the years, as well as completely new entities that appear for the first time at some point. Thus, we enable to quantify the performance of current state-of-the-art EL models for: (i) entities that are subject to changes over time in their Knowledge Base descriptions as well as their mentions' contexts, and (ii) newly created entities that were previously non-existing (e.g., at the time the EL model was trained). Our experimental results show that in terms of temporal performance degradation, (i) continual entities suffer a decrease of up to 3.1% EL accuracy, while (ii) for new entities this accuracy drop is up to 17.9%. This highlights the challenge of the introduced TempEL dataset and opens new research prospects in the area of time-evolving entity disambiguation.
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- 2023
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28. CEBaB: Estimating the Causal Effects of Real-World Concepts on NLP Model Behavior
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Abraham, E. D., D'Oosterlinck, Karel, Feder, A., Gat, Y., Geiger, A., Potts, C., Reichart, R., Wu, Z., Koyejo, S., Mohamed, S., Agarwal, A., Belgrave, D., Cho, K., and Oh, A.
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FOS: Computer and information sciences ,Technology and Engineering ,Computer Science - Computation and Language ,Computation and Language (cs.CL) - Abstract
The increasing size and complexity of modern ML systems has improved their predictive capabilities but made their behavior harder to explain. Many techniques for model explanation have been developed in response, but we lack clear criteria for assessing these techniques. In this paper, we cast model explanation as the causal inference problem of estimating causal effects of real-world concepts on the output behavior of ML models given actual input data. We introduce CEBaB, a new benchmark dataset for assessing concept-based explanation methods in Natural Language Processing (NLP). CEBaB consists of short restaurant reviews with human-generated counterfactual reviews in which an aspect (food, noise, ambiance, service) of the dining experience was modified. Original and counterfactual reviews are annotated with multiply-validated sentiment ratings at the aspect-level and review-level. The rich structure of CEBaB allows us to go beyond input features to study the effects of abstract, real-world concepts on model behavior. We use CEBaB to compare the quality of a range of concept-based explanation methods covering different assumptions and conceptions of the problem, and we seek to establish natural metrics for comparative assessments of these methods., Accepted to NeurIPS 2022
- Published
- 2022
29. Evaluating Robustness to Dataset Shift via Parametric Robustness Sets
- Author
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Thams, Nikolaj, Oberst, Michael, Sontag, David, Koyejo, S., Mohamed, S., Agarwal, A., Belgrave, D., Cho, K., and Oh, A.
- Abstract
We give a method for proactively identifying small, plausible shifts in distribution which lead to large differences in model performance. These shifts are defined via parametric changes in the causal mechanisms of observed variables, where constraints on parameters yield a “robustness set” of plausible distributions and a corresponding worst-case loss over the set. While the loss under an individual parametric shift can be estimated via reweighting techniques such as importance sampling, the resulting worst-case optimization problem is non-convex, and the estimate may suffer from large variance. For small shifts, however, we can construct a local second-order approximation to the loss under shift and cast the problem of finding a worst-case shift as a particular non-convex quadratic optimization problem, for which efficient algorithms are available. We demonstrate that this second-order approximation can be estimated directly for shifts in conditional exponential family models, and we bound the approximation error. We apply our approach to a computer vision task (classifying gender from images), revealing sensitivity to shifts in non-causal attributes.
- Published
- 2022
30. Provably expressive temporal graph networks
- Author
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Souza, Amauri H., Mesquita, Diego, Kaski, Samuel, Garg, Vikas, Koyejo, S., Mohamed, S., Agarwal, A., Belgrave, D., Cho, K., Oh, A., Department of Computer Science, Computer Science Professors, Aalto-yliopisto, and Aalto University
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FOS: Computer and information sciences ,Computer Science - Machine Learning ,Machine Learning (cs.LG) - Abstract
Temporal graph networks (TGNs) have gained prominence as models for embedding dynamic interactions, but little is known about their theoretical underpinnings. We establish fundamental results about the representational power and limits of the two main categories of TGNs: those that aggregate temporal walks (WA-TGNs), and those that augment local message passing with recurrent memory modules (MP-TGNs). Specifically, novel constructions reveal the inadequacy of MP-TGNs and WA-TGNs, proving that neither category subsumes the other. We extend the 1-WL (Weisfeiler-Leman) test to temporal graphs, and show that the most powerful MP-TGNs should use injective updates, as in this case they become as expressive as the temporal WL. Also, we show that sufficiently deep MP-TGNs cannot benefit from memory, and MP/WA-TGNs fail to compute graph properties such as girth. These theoretical insights lead us to PINT -- a novel architecture that leverages injective temporal message passing and relative positional features. Importantly, PINT is provably more expressive than both MP-TGNs and WA-TGNs. PINT significantly outperforms existing TGNs on several real-world benchmarks., Comment: Accepted to NeurIPS 2022
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- 2022
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31. Deconfounded Representation Similarity for Comparison of Neural Networks
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Cui, Tianyu, Kumar, Yogesh, Marttinen, Pekka, Kaski, Samuel, Koyejo, S., Mohamed, S., Agarwal, A., Belgrave, D., Cho, K., Oh, A., Department of Computer Science, Professorship Marttinen P., Computer Science Professors, Aalto-yliopisto, and Aalto University
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FOS: Computer and information sciences ,Deep Neural Networks ,Computer Science - Machine Learning ,Statistics - Machine Learning ,representation similarity ,functional similarity ,covariate adjustment regression ,Machine Learning (stat.ML) ,Machine Learning (cs.LG) - Abstract
openaire: EC/H2020/951847/EU//ELISE | openaire: EC/H2020/101016775/EU//INTERVENE Similarity metrics such as representational similarity analysis (RSA) and centered kernel alignment (CKA) have been used to understand neural networks by comparing their layer-wise representations. However, these metrics are confounded by the population structure of data items in the input space, leading to inconsistent conclusions about the \emph{functional} similarity between neural networks, such as spuriously high similarity of completely random neural networks and inconsistent domain relations in transfer learning. We introduce a simple and generally applicable fix to adjust for the confounder with covariate adjustment regression, which improves the ability of CKA and RSA to reveal functional similarity and also retains the intuitive invariance properties of the original similarity measures. We show that deconfounding the similarity metrics increases the resolution of detecting functionally similar neural networks across domains. Moreover, in real-world applications, deconfounding improves the consistency between CKA and domain similarity in transfer learning, and increases the correlation between CKA and model out-of-distribution accuracy similarity.
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- 2022
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32. Optimal Transport of Classifiers to Fairness
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Buyl, Maarten, De Bie, Tijl, Koyejo, S., Mohamed, S., Agarwal, A., Belgrave, D., Cho, K., and Oh, A.
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FOS: Computer and information sciences ,Computer Science - Machine Learning ,Technology and Engineering ,Statistics - Machine Learning ,Machine Learning (stat.ML) ,Machine Learning (cs.LG) - Abstract
In past work on fairness in machine learning, the focus has been on forcing the prediction of classifiers to have similar statistical properties for people of different demographics. To reduce the violation of these properties, fairness methods usually simply rescale the classifier scores, ignoring similarities and dissimilarities between members of different groups. Yet, we hypothesize that such information is relevant in quantifying the unfairness of a given classifier. To validate this hypothesis, we introduce Optimal Transport to Fairness (OTF), a method that quantifies the violation of fairness constraints as the smallest Optimal Transport cost between a probabilistic classifier and any score function that satisfies these constraints. For a flexible class of linear fairness constraints, we construct a practical way to compute OTF as a differentiable fairness regularizer that can be added to any standard classification setting. Experiments show that OTF can be used to achieve an improved trade-off between predictive power and fairness.
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- 2022
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33. Gaussian Copula Embeddings
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Lu, Chien, Peltonen, Jaakko, Koyejo, S., Mohamed, S., Agarwal , A., Belgrave, D., Cho, K., Oh, A., Tampere University, Communication Sciences, and Computing Sciences
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113 Computer and information sciences - Abstract
acceptedVersion
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- 2022
34. A Multilabel Classification Framework for Approximate Nearest Neighbor Search
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Hyvönen, Ville, Jääsaari, Elias, Roos, Teemu, Koyejo, S, Mohamed, S, Agarwal, A, Belgrave, D, Cho, K, Oh, A, Department of Computer Science, Complex Systems Computation Group, and Helsinki Institute for Information Technology
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Computer Science::Machine Learning ,FOS: Computer and information sciences ,Computer Science - Machine Learning ,ComputingMethodologies_PATTERNRECOGNITION ,G.3 ,H.3.3 ,Statistics - Machine Learning ,Machine Learning (stat.ML) ,113 Computer and information sciences ,Machine Learning (cs.LG) - Abstract
Both supervised and unsupervised machine learning algorithms have been used to learn partition-based index structures for approximate nearest neighbor (ANN) search. Existing supervised algorithms formulate the learning task as finding a partition in which the nearest neighbors of a training set point belong to the same partition element as the point itself, so that the nearest neighbor candidates can be retrieved by naive lookup or backtracking search. We formulate candidate set selection in ANN search directly as a multilabel classification problem where the labels correspond to the nearest neighbors of the query point, and interpret the partitions as partitioning classifiers for solving this task. Empirical results suggest that the natural classifier based on this interpretation leads to strictly improved performance when combined with any unsupervised or supervised partitioning strategy. We also prove a sufficient condition for consistency of a partitioning classifier for ANN search, and illustrate the result by verifying this condition for chronological $k$-d trees., Comment: To appear in the proceedings of Conference on Neural Information Processing Systems (NeurIPS) 2022
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- 2019
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35. Generative models improve fairness of medical classifiers under distribution shifts.
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Ktena I, Wiles O, Albuquerque I, Rebuffi SA, Tanno R, Roy AG, Azizi S, Belgrave D, Kohli P, Cemgil T, Karthikesalingam A, and Gowal S
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- Artificial Intelligence, Machine Learning
- Abstract
Domain generalization is a ubiquitous challenge for machine learning in healthcare. Model performance in real-world conditions might be lower than expected because of discrepancies between the data encountered during deployment and development. Underrepresentation of some groups or conditions during model development is a common cause of this phenomenon. This challenge is often not readily addressed by targeted data acquisition and 'labeling' by expert clinicians, which can be prohibitively expensive or practically impossible because of the rarity of conditions or the available clinical expertise. We hypothesize that advances in generative artificial intelligence can help mitigate this unmet need in a steerable fashion, enriching our training dataset with synthetic examples that address shortfalls of underrepresented conditions or subgroups. We show that diffusion models can automatically learn realistic augmentations from data in a label-efficient manner. We demonstrate that learned augmentations make models more robust and statistically fair in-distribution and out of distribution. To evaluate the generality of our approach, we studied three distinct medical imaging contexts of varying difficulty: (1) histopathology, (2) chest X-ray and (3) dermatology images. Complementing real samples with synthetic ones improved the robustness of models in all three medical tasks and increased fairness by improving the accuracy of clinical diagnosis within underrepresented groups, especially out of distribution., (© 2024. The Author(s).)
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- 2024
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36. Deep learning for the prediction of clinical outcomes in internet-delivered CBT for depression and anxiety.
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Prasad N, Chien I, Regan T, Enrique A, Palacios J, Keegan D, Munir U, Tanno R, Richardson H, Nori A, Richards D, Doherty G, Belgrave D, and Thieme A
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- Humans, Depression therapy, Depression psychology, Anxiety Disorders therapy, Anxiety Disorders psychology, Anxiety therapy, Anxiety psychology, Internet, Treatment Outcome, Deep Learning, Cognitive Behavioral Therapy methods
- Abstract
In treating depression and anxiety, just over half of all clients respond. Monitoring and obtaining early client feedback can allow for rapidly adapted treatment delivery and improve outcomes. This study seeks to develop a state-of-the-art deep-learning framework for predicting clinical outcomes in internet-delivered Cognitive Behavioural Therapy (iCBT) by leveraging large-scale, high-dimensional time-series data of client-reported mental health symptoms and platform interaction data. We use de-identified data from 45,876 clients on SilverCloud Health, a digital platform for the psychological treatment of depression and anxiety. We train deep recurrent neural network (RNN) models to predict whether a client will show reliable improvement by the end of treatment using clinical measures, interaction data with the iCBT program, or both. Outcomes are based on total improvement in symptoms of depression (Patient Health Questionnaire-9, PHQ-9) and anxiety (Generalized Anxiety Disorder-7, GAD-7), as reported within the iCBT program. Using internal and external datasets, we compare the proposed models against several benchmarks and rigorously evaluate them according to their predictive accuracy, sensitivity, specificity and AUROC over treatment. Our proposed RNN models consistently predict reliable improvement in PHQ-9 and GAD-7, using past clinical measures alone, with above 87% accuracy and 0.89 AUROC after three or more review periods, outperforming all benchmark models. Additional evaluations demonstrate the robustness of the achieved models across (i) different health services; (ii) geographic locations; (iii) iCBT programs, and (iv) client severity subgroups. Results demonstrate the robust performance of dynamic prediction models that can yield clinically helpful prognostic information ready for implementation within iCBT systems to support timely decision-making and treatment adjustments by iCBT clinical supporters towards improved client outcomes., Competing Interests: AE, JP, DK, and DR are employees of SilverCloud Health. GD is a cofounder of SilverCloud Health and has a minority shareholding in the company. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Prasad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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37. The promise of machine learning in predicting treatment outcomes in psychiatry.
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Chekroud AM, Bondar J, Delgadillo J, Doherty G, Wasil A, Fokkema M, Cohen Z, Belgrave D, DeRubeis R, Iniesta R, Dwyer D, and Choi K
- Abstract
For many years, psychiatrists have tried to understand factors involved in response to medications or psychotherapies, in order to personalize their treatment choices. There is now a broad and growing interest in the idea that we can develop models to personalize treatment decisions using new statistical approaches from the field of machine learning and applying them to larger volumes of data. In this pursuit, there has been a paradigm shift away from experimental studies to confirm or refute specific hypotheses towards a focus on the overall explanatory power of a predictive model when tested on new, unseen datasets. In this paper, we review key studies using machine learning to predict treatment outcomes in psychiatry, ranging from medications and psychotherapies to digital interventions and neurobiological treatments. Next, we focus on some new sources of data that are being used for the development of predictive models based on machine learning, such as electronic health records, smartphone and social media data, and on the potential utility of data from genetics, electrophysiology, neuroimaging and cognitive testing. Finally, we discuss how far the field has come towards implementing prediction tools in real-world clinical practice. Relatively few retrospective studies to-date include appropriate external validation procedures, and there are even fewer prospective studies testing the clinical feasibility and effectiveness of predictive models. Applications of machine learning in psychiatry face some of the same ethical challenges posed by these techniques in other areas of medicine or computer science, which we discuss here. In short, machine learning is a nascent but important approach to improve the effectiveness of mental health care, and several prospective clinical studies suggest that it may be working already., (© 2021 World Psychiatric Association.)
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- 2021
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38. A Machine Learning Approach to Understanding Patterns of Engagement With Internet-Delivered Mental Health Interventions.
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Chien I, Enrique A, Palacios J, Regan T, Keegan D, Carter D, Tschiatschek S, Nori A, Thieme A, Richards D, Doherty G, and Belgrave D
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- Adult, Anxiety psychology, Anxiety therapy, Cognitive Behavioral Therapy methods, Cohort Studies, Depression psychology, Depression therapy, Female, Humans, Internet, Machine Learning statistics & numerical data, Male, Mental Health Services statistics & numerical data, Patient Health Questionnaire statistics & numerical data, Patient Participation statistics & numerical data, Telemedicine methods, Telemedicine statistics & numerical data, Machine Learning standards, Mental Health Services standards, Patient Participation psychology, Telemedicine standards
- Abstract
Importance: The mechanisms by which engagement with internet-delivered psychological interventions are associated with depression and anxiety symptoms are unclear., Objective: To identify behavior types based on how people engage with an internet-based cognitive behavioral therapy (iCBT) intervention for symptoms of depression and anxiety., Design, Setting, and Participants: Deidentified data on 54 604 adult patients assigned to the Space From Depression and Anxiety treatment program from January 31, 2015, to March 31, 2019, were obtained for probabilistic latent variable modeling using machine learning techniques to infer distinct patient subtypes, based on longitudinal heterogeneity of engagement patterns with iCBT., Interventions: A clinician-supported iCBT-based program that follows clinical guidelines for treating depression and anxiety, delivered on a web 2.0 platform., Main Outcomes and Measures: Log data from user interactions with the iCBT program to inform engagement patterns over time. Clinical outcomes included symptoms of depression (Patient Health Questionnaire-9 [PHQ-9]) and anxiety (Generalized Anxiety Disorder-7 [GAD-7]); PHQ-9 cut point greater than or equal to 10 and GAD-7 scores greater than or equal to 8 were used to define depression and anxiety., Results: Patients spent a mean (SD) of 111.33 (118.92) minutes on the platform and completed 230.60 (241.21) tools. At baseline, mean PHQ-9 score was 12.96 (5.81) and GAD-7 score was 11.85 (5.14). Five subtypes of engagement were identified based on patient interaction with different program sections over 14 weeks: class 1 (low engagers, 19 930 [36.5%]), class 2 (late engagers, 11 674 [21.4%]), class 3 (high engagers with rapid disengagement, 13 936 [25.5%]), class 4 (high engagers with moderate decrease, 3258 [6.0%]), and class 5 (highest engagers, 5799 [10.6%]). Estimated mean decrease (SE) in PHQ-9 score was 6.65 (0.14) for class 3, 5.88 (0.14) for class 5, and 5.39 (0.14) for class 4; class 2 had the lowest rate of decrease at -4.41 (0.13). Compared with PHQ-9 score decrease in class 1, the Cohen d effect size (SE) was -0.46 (0.014) for class 2, -0.46 (0.014) for class 3, -0.61 (0.021) for class 4, and -0.73 (0.018) for class 5. Similar patterns were found across groups for GAD-7., Conclusions and Relevance: The findings of this study may facilitate tailoring interventions according to specific subtypes of engagement for individuals with depression and anxiety. Informing clinical decision needs of supporters may be a route to successful adoption of machine learning insights, thus improving clinical outcomes overall.
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- 2020
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39. Early-life inhalant allergen exposure, filaggrin genotype, and the development of sensitization from infancy to adolescence.
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Simpson A, Brough HA, Haider S, Belgrave D, Murray CS, and Custovic A
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- Adolescent, Air Pollution, Indoor adverse effects, Allergens adverse effects, Animals, Antigens, Dermatophagoides adverse effects, Arthropod Proteins adverse effects, Cats, Child, Child, Preschool, Cohort Studies, Cross-Sectional Studies, Cysteine Endopeptidases adverse effects, Dogs, Environmental Exposure adverse effects, Female, Filaggrin Proteins, Genotype, Glycoproteins adverse effects, Humans, Hypersensitivity immunology, Infant, Infant, Newborn, Male, Mutation, Pyroglyphidae immunology, Allergens immunology, Antigens, Dermatophagoides immunology, Arthropod Proteins immunology, Cysteine Endopeptidases immunology, Genetic Predisposition to Disease genetics, Glycoproteins immunology, Hypersensitivity genetics, S100 Proteins genetics
- Abstract
Background: We hypothesized that filaggrin (FLG) loss-of-function mutations modify the effect of allergen exposure on the development of allergic sensitization., Objective: We sought to determine whether early-life exposure to inhalant allergens increases the risk of specific sensitization and whether FLG mutations modulate these odds., Methods: In a population-based birth cohort we measured mite, cat, and dog allergen levels in dust samples collected from homes within the first year of life. Sensitization was assessed at 6 time points between infancy and age 16 years. Genotyping was performed for 6 FLG mutations., Results: In the longitudinal multivariable model (age 1-16 years), we observed a significant interaction between FLG and Fel d 1 exposure on cat sensitization, with the effect of exposure being significantly greater among children with FLG mutations compared with those without (odds ratio, 1.36; 95% CI, 1.02-1.80; P = .035). The increase in risk of mite sensitization with increasing Der p 1 exposure was consistently greater among children with FLG mutations, but the interaction did not reach statistical significance. Different associations were observed for dogs: there was a significant interaction between FLG and dog ownership, but the risk of sensitization to any allergen was significantly lower among children with FLG mutations who were exposed to a dog in infancy (odds ratio, 0.16; 95% CI, 0.03-0.86; P = .03)., Conclusions: FLG loss-of-function mutations modify the relationship between allergen exposure and sensitization, but effects differ at different ages and between different allergens., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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40. Differential associations of allergic disease genetic variants with developmental profiles of eczema, wheeze and rhinitis.
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Clark H, Granell R, Curtin JA, Belgrave D, Simpson A, Murray C, Henderson AJ, Custovic A, and Paternoster L
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- Child, Female, Filaggrin Proteins, Genome-Wide Association Study, Humans, Longitudinal Studies, Male, Eczema genetics, Hypersensitivity genetics, Polymorphism, Single Nucleotide, Respiratory Sounds genetics, Rhinitis genetics
- Abstract
Background: Allergic diseases (eczema, wheeze and rhinitis) in children often present as heterogeneous phenotypes. Understanding genetic associations of specific patterns of symptoms might facilitate understanding of the underlying biological mechanisms., Objective: To examine associations between allergic disease-related variants identified in a recent genome-wide association study and latent classes of allergic diseases (LCADs) in two population-based birth cohorts., Methods: Eight previously defined LCADs between birth and 11 years: "No disease," "Atopic march," "Persistent eczema and wheeze," "Persistent eczema with later-onset rhinitis," "Persistent wheeze with later-onset rhinitis," "Transient wheeze," "Eczema only" and "Rhinitis only" were used as the study outcome. Weighted multinomial logistic regression was used to estimate associations between 135 SNPs (and a polygenic risk score, PRS) and LCADs among 6345 individuals from The Avon Longitudinal Study of Parents and Children (ALSPAC). Heterogeneity across LCADs was assessed before and after Bonferroni correction. Results were replicated in Manchester Asthma and Allergy Study (MAAS) (n = 896) and pooled in a meta-analysis., Results: We found strong evidence for differential genetic associations across the LCADs; pooled PRS heterogeneity P-value = 3.3 × 10
-14 , excluding "no disease" class. The associations between the PRS and LCADs in MAAS were remarkably similar to ALSPAC. Two SNPs (a protein-truncating variant in FLG and a SNP within an intron of GSDMB) had evidence for differential association (pooled P-values ≤ 0.006). The FLG locus was differentially associated across LCADs that included eczema, with stronger associations for LCADs with comorbid wheeze and rhinitis. The GSDMB locus in contrast was equally associated across LCADs that included wheeze., Conclusions and Clinical Relevance: We have shown complex, but distinct patterns of genetic associations with LCADs, suggesting that heterogeneous mechanisms underlie individual disease trajectories. Establishing the combination of allergic diseases with which each genetic variant is associated may inform therapeutic development and/or predictive modelling., (© 2019 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)- Published
- 2019
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41. Temporal association of the development of oropharyngeal microbiota with early life wheeze in a population-based birth cohort.
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Powell EA, Fontanella S, Boakes E, Belgrave D, Shaw AG, Cornwell E, Fernandez-Crespo R, Fink CG, Custovic A, and Kroll JS
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- Age Factors, Biodiversity, Cohort Studies, Female, Humans, Male, Metagenome, Metagenomics methods, Population Surveillance, United Kingdom epidemiology, Microbiota, Oropharynx microbiology, Respiratory Sounds etiology
- Abstract
Background: A critical window in infancy has been proposed, during which the microbiota may affect subsequent health. The longitudinal development of the oropharyngeal microbiota is under-studied and may be associated with early-life wheeze. We aimed to investigate the temporal association of the development of the oropharyngeal microbiota with early-life wheeze., Methods: A population-based birth cohort based in London, UK was followed for 24 months. We collected oropharyngeal swabs at six time-points. Microbiota was determined using sequencing of the V3-V5 region of the 16S rRNA-encoding gene. Medical records were reviewed for the outcome of doctor diagnosed wheeze. We used a time-varying model to investigate the temporal association between the development of microbiota and doctor-diagnosed wheeze., Findings: 159 participants completed the study to 24 months and for 98 there was complete sequencing data at all timepoints and outcome data. Of these, 26 had doctor-diagnosed wheeze. We observed significant increase in the abundance of Neisseria between 9 and 24 months in children who developed wheeze (p = 0∙003), while in those without wheezing there was a significant increment in the abundance of Granulicatella (p = 0∙012) between 9 and 12 months, and of Prevotella (p = 0∙018) after 18 months., Interpretation: A temporal association between the respiratory commensal Granulicatella and also Prevotella with wheeze (negative), and between Neisseria and wheeze (positive) was identified in infants prior to one year of age. This adds to evidence for the proposed role of the microbiota in the development of wheeze. FUND: Research funding from the Winnicott Foundation, Meningitis Now and Micropathology Ltd., (Copyright © 2019. Published by Elsevier B.V.)
- Published
- 2019
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42. Individual risk assessment tool for school-age asthma prediction in UK birth cohort.
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Wang R, Simpson A, Custovic A, Foden P, Belgrave D, and Murray CS
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- Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Infant, Newborn, Male, Predictive Value of Tests, Risk Assessment, United Kingdom epidemiology, Asthma epidemiology, Asthma immunology, Asthma physiopathology, Models, Biological
- Abstract
Background: Current published asthma predictive tools have moderate positive likelihood ratios (+LR) but high negative likelihood ratios (-LR) based on their recommended cut-offs, which limit their clinical usefulness., Objective: To develop a simple clinically applicable asthma prediction tool within a population-based birth cohort., Method: Children from the Manchester Asthma and Allergy Study (MAAS) attended follow-up at ages 3, 8 and 11 years. Data on preschool wheeze were extracted from primary-care records. Parents completed validated respiratory questionnaires. Children were skin prick tested (SPT). Asthma at 8/11 years (school-age) was defined as parentally reported (a) physician-diagnosed asthma and wheeze in the previous 12 months or (b) ≥3 wheeze attacks in the previous 12 months. An asthma prediction tool (MAAS APT) was developed using logistic regression of characteristics at age 3 years to predict school-age asthma., Results: Of 336 children with physician-confirmed wheeze by age 3 years, 117(35%) had school-age asthma. Logistic regression selected 5 significant risk factors which formed the basis of the MAAS APT: wheeze after exercise; wheeze causing breathlessness; cough on exertion; current eczema and SPT sensitisation(maximum score 5). A total of 281(84%) children had complete data at age 3 years and were used to test the MAAS APT. Children scoring ≥3 were at high risk of having asthma at school-age (PPV > 75%; +LR 6.3, -LR 0.6), whereas children who had a score of 0 had very low risk(PPV 9.3%; LR 0.2)., Conclusion: MAAS APT is a simple asthma prediction tool which could easily be applied in clinical and research settings., (© 2018 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.)
- Published
- 2019
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43. Evolution of IgE responses to multiple allergen components throughout childhood.
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Howard R, Belgrave D, Papastamoulis P, Simpson A, Rattray M, and Custovic A
- Subjects
- Adolescent, Bayes Theorem, Child, Child, Preschool, Humans, Infant, Male, Allergens immunology, Asthma immunology, Immunoglobulin E immunology, Rhinitis immunology
- Abstract
Background: There is a paucity of information about longitudinal patterns of IgE responses to allergenic proteins (components) from multiple sources., Objectives: This study sought to investigate temporal patterns of component-specific IgE responses from infancy to adolescence, and their relationship with allergic diseases., Methods: In a population-based birth cohort, we measured IgE to 112 components at 6 follow-ups during childhood. We used a Bayesian method to discover cross-sectional sensitization patterns and their longitudinal trajectories, and we related these patterns to asthma and rhinitis in adolescence., Results: We identified 1 sensitization cluster at age 1, 3 at age 3, 4 at ages 5 and 8, 5 at age 11, and 6 at age 16 years. "Broad" cluster was the only cluster present at every follow-up, comprising components from multiple sources. "Dust mite" cluster formed at age 3 years and remained unchanged to adolescence. At age 3 years, a single-component "Grass" cluster emerged, which at age 5 years absorbed additional grass components and Fel d 1 to form the "Grass/cat" cluster. Two new clusters formed at age 11 years: "Cat" cluster and "PR-10/profilin" (which divided at age 16 years into "PR-10" and "Profilin"). The strongest contemporaneous associate of asthma at age 16 years was sensitization to dust mite cluster (odds ratio: 2.6; 95% CI: 1.2-6.1; P < .05), but the strongest early life predictor of subsequent asthma was sensitization to grass/cat cluster (odds ratio: 3.5; 95% CI: 1.6-7.4; P < .01)., Conclusions: We describe the architecture of the evolution of IgE responses to multiple allergen components throughout childhood, which may facilitate development of better diagnostic and prognostic biomarkers for allergic diseases., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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44. Cytokine Responses to Rhinovirus and Development of Asthma, Allergic Sensitization, and Respiratory Infections during Childhood.
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Custovic A, Belgrave D, Lin L, Bakhsoliani E, Telcian AG, Solari R, Murray CS, Walton RP, Curtin J, Edwards MR, Simpson A, Rattray M, and Johnston SL
- Subjects
- Adolescent, Antiviral Agents immunology, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Male, Picornaviridae Infections immunology, Respiratory Tract Infections immunology, Antiviral Agents therapeutic use, Asthma drug therapy, Cytokines immunology, Picornaviridae Infections drug therapy, Respiratory Tract Infections drug therapy, Rhinovirus drug effects, Rhinovirus immunology
- Abstract
Rationale: Immunophenotypes of antiviral responses, and their relationship with asthma, allergy, and lower respiratory tract infections, are poorly understood., Objectives: We characterized multiple cytokine responses of peripheral blood mononuclear cells to rhinovirus stimulation, and their relationship with clinical outcomes., Methods: In a population-based birth cohort, we measured 28 cytokines after stimulation with rhinovirus-16 in 307 children aged 11 years. We used machine learning to identify patterns of cytokine responses, and related these patterns to clinical outcomes, using longitudinal models. We also ascertained phytohemagglutinin-induced T-helper cell type 2 (Th2)-cytokine responses (PHA-Th2)., Measurements and Main Results: We identified six clusters of children based on their rhinovirus-16 responses, which were differentiated by the expression of four cytokine/chemokine groups: interferon-related (IFN), proinflammatory (Inflam), Th2-chemokine (Th2-chem), and regulatory (Reg). Clusters differed in their clinical characteristics. Children with an IFN
mod Inflamhighest Th2-chemhighest Reghighest rhinovirus-16-induced pattern had a PHA-Th2low response, and a very low asthma risk (odds ratio [OR], 0.08; 95% confidence interval [CI], 0.01-0.81; P = 0.03). Two clusters had a high risk of asthma and allergic sensitization, but with different trajectories from infancy to adolescence. The IFNlowest Inflamhigh Th2-chemlow Regmod cluster exhibited a PHA-Th2lowest response and was associated with early-onset asthma and sensitization, and the highest risk of asthma exacerbations (OR, 1.37; 95% CI, 1.07-1.76; P = 0.014) and lower respiratory tract infection hospitalizations (OR, 2.40; 95% CI, 1.26-4.58; P = 0.008) throughout childhood. In contrast, the IFNhighest Inflammod Th2-chemmod Reghigh cluster with a rhinovirus-16-cytokine pattern was characterized by a PHA-Th2highest response, and a low prevalence of asthma/sensitization in infancy that increased sharply to become the highest among all clusters by adolescence (but with a low risk of asthma exacerbations)., Conclusions: Early-onset troublesome asthma with early-life sensitization, later-onset milder allergic asthma, and disease protection are each associated with different patterns of rhinovirus-induced immune responses.- Published
- 2018
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45. Detection of IgE Reactivity to a Handful of Allergen Molecules in Early Childhood Predicts Respiratory Allergy in Adolescence.
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Wickman M, Lupinek C, Andersson N, Belgrave D, Asarnoj A, Benet M, Pinart M, Wieser S, Garcia-Aymerich J, Baar A, Pershagen G, Simpson A, Kull I, Bergström A, Melén E, Hamsten C, Antó JM, Bousquet J, Custovic A, Valenta R, and van Hage M
- Subjects
- Allergens immunology, Antigens, Dermatophagoides adverse effects, Antigens, Dermatophagoides immunology, Arthropod Proteins adverse effects, Arthropod Proteins immunology, Asthma blood, Asthma etiology, Child, Child, Preschool, Cysteine Endopeptidases adverse effects, Cysteine Endopeptidases immunology, Female, Humans, Hypersensitivity etiology, Hypersensitivity pathology, Immunoglobulin E blood, Male, Rhinitis, Allergic etiology, Rhinitis, Allergic pathology, Allergens adverse effects, Asthma immunology, Hypersensitivity immunology, Immunoglobulin E immunology, Rhinitis, Allergic immunology
- Abstract
Background: Sensitization in early childhood may precede respiratory allergy in adolescence., Methods: IgE reactivity against 132 allergen molecules was evaluated using the MeDALL microarray in sera obtained from a random sample of 786 children at the age of 4, 8 and 16years in a population based birth cohort (BAMSE). Symptoms were analyzed by questionnaire at ages 4, 8 and 16years. Clinically and independent relevant allergen molecules accounting for ≥90% of IgE reactivities in sensitized individuals and at all time-points were identified as risk molecules and used to predict respiratory allergy. The data was replicated in the Manchester Asthma and Allergy Study (MAAS) birth cohort by studying IgE reactivity with the use of a commercial IgE microarray. Sera were obtained from children at the ages of 3, 5, 8 and 11years (N=248) and the outcome was studied at 11years., Findings: In the BAMSE cohort 4 risk molecules could be identified, i.e.: Ara h 1 (peanut), Bet v 1 (birch), Fel d 1 (cat), Phl p 1 (grass). For MAAS the corresponding number of molecules was 5: Der p 1 (dust mite), Der f 2 (dust mite), Phl p 1 (grass), Phl p 5 (grass), Fel d 1 (cat). In BAMSE, early IgE reactivity to ≥3 of 4 allergen molecules at four years predicted incident and persistent asthma and/or rhinitis at 16years (87% and 95%, respectively). The corresponding proportions in the MAAS cohort at 16years were 100% and 100%, respectively, for IgE reactivity to ≥3 of 5 risk molecules., Interpretations: IgE reactivity to a few allergen molecules early in life identifies children with a high risk of asthma and/or rhinitis at 16years. These findings will be of importance for developing preventive strategies for asthma and rhinitis in children., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)
- Published
- 2017
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46. Asthma phenotypes in childhood.
- Author
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Deliu M, Belgrave D, Sperrin M, Buchan I, and Custovic A
- Subjects
- Asthma therapy, Child, Disease Management, Humans, Patient Selection, Precision Medicine, Asthma physiopathology, Phenotype
- Abstract
Introduction: Asthma is no longer thought of as a single disease, but rather a collection of varying symptoms expressing different disease patterns. One of the ongoing challenges is understanding the underlying pathophysiological mechanisms that may be responsible for the varying responses to treatment. Areas Covered: This review provides an overview of our current understanding of the asthma phenotype concept in childhood and describes key findings from both conventional and data-driven methods. Expert Commentary: With the vast amounts of data generated from cohorts, there is hope that we can elucidate distinct pathophysiological mechanisms, or endotypes. In return, this would lead to better patient stratification and disease management, thereby providing true personalised medicine.
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- 2017
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47. Disaggregating asthma: Big investigation versus big data.
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Belgrave D, Henderson J, Simpson A, Buchan I, Bishop C, and Custovic A
- Subjects
- Asthma immunology, Computational Biology, Delivery of Health Care, Humans, Interdisciplinary Communication, Phenotype, Precision Medicine, Software, United Kingdom epidemiology, Asthma epidemiology, Electronic Data Processing, Translational Research, Biomedical
- Abstract
We are facing a major challenge in bridging the gap between identifying subtypes of asthma to understand causal mechanisms and translating this knowledge into personalized prevention and management strategies. In recent years, "big data" has been sold as a panacea for generating hypotheses and driving new frontiers of health care; the idea that the data must and will speak for themselves is fast becoming a new dogma. One of the dangers of ready accessibility of health care data and computational tools for data analysis is that the process of data mining can become uncoupled from the scientific process of clinical interpretation, understanding the provenance of the data, and external validation. Although advances in computational methods can be valuable for using unexpected structure in data to generate hypotheses, there remains a need for testing hypotheses and interpreting results with scientific rigor. We argue for combining data- and hypothesis-driven methods in a careful synergy, and the importance of carefully characterized birth and patient cohorts with genetic, phenotypic, biological, and molecular data in this process cannot be overemphasized. The main challenge on the road ahead is to harness bigger health care data in ways that produce meaningful clinical interpretation and to translate this into better diagnoses and properly personalized prevention and treatment plans. There is a pressing need for cross-disciplinary research with an integrative approach to data science, whereby basic scientists, clinicians, data analysts, and epidemiologists work together to understand the heterogeneity of asthma., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2017
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48. The importance of being earnest in epidemiology.
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Belgrave D and Custovic A
- Subjects
- Child, Humans, Epidemiologic Methods, Hypersensitivity
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- 2016
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49. Age, sex and the association between skin test responses and IgE titres with asthma.
- Author
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Mohammad HR, Belgrave D, Kopec Harding K, Murray CS, Simpson A, and Custovic A
- Subjects
- Age Factors, Asthma immunology, Child, Child, Preschool, Female, Humans, Male, Prospective Studies, Sex Factors, Skin Tests statistics & numerical data, Asthma diagnosis, Immunoglobulin E blood, Respiratory Sounds immunology, Skin Tests methods
- Abstract
Background: Skin prick tests (SPTs) and allergen-specific serum IgE (sIgE) measurements are the main diagnostic tools for confirming atopic sensitization. Results are usually reported as 'positive' or 'negative', using the same arbitrary cut-offs (SPT>3 mm, sIgE>0.35 kUA /l) across different ages and sexes. We investigated the influence of age and sex on the interpretation of allergy test in the context of childhood asthma., Methods: In a population-based birth cohort (n = 1051), we ascertained the information on asthma/wheeze (validated questionnaires) and performed SPTs and sIgE measurement to inhalant allergens (dust mite, cat, dog) at follow-ups between ages three and 11 years. We investigated the association between quantitative sensitization (sum of SPT mean wheal diameters [MWD] and sIgE titres to the three allergens) and current wheeze and asthma across ages and sexes., Results: We observed a significant association between the SPT MWD and sIgE titres and wheeze/asthma at most ages and for both sexes. However, the strength of this association was age- and sex-dependent. For SPTs, the strength of the association between MWD and asthma increased with increasing age; we observed the opposite pattern for sIgE titre. For any given SPT MWD/sIgE titre, boys were significantly more likely to express clinical symptoms, particularly in early life; this difference between males and females diminished with age and was no longer significant by age 11 years., Conclusions: Age and sex should be taken into account when interpreting the results of skin tests and sIgE measurement, and age- and sex-specific normative data are needed for these allergy tests., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2016
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50. Distinguishing benign from pathologic TH2 immunity in atopic children.
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Holt PG, Strickland D, Bosco A, Belgrave D, Hales B, Simpson A, Hollams E, Holt B, Kusel M, Ahlstedt S, Sly PD, and Custovic A
- Subjects
- Adolescent, Allergens immunology, Animals, Antibody Specificity immunology, Asthma diagnosis, Asthma genetics, Asthma immunology, Asthma metabolism, Basophils immunology, Basophils metabolism, Child, Child, Preschool, Cytokines metabolism, Female, Gene Expression Profiling, Humans, Hypersensitivity, Immediate diagnosis, Hypersensitivity, Immediate genetics, Hypersensitivity, Immediate metabolism, Immunoglobulin E blood, Immunoglobulin E immunology, Immunoglobulin G blood, Immunoglobulin G immunology, Immunologic Memory, Male, Phenotype, Poaceae adverse effects, Pyroglyphidae immunology, Severity of Illness Index, Th2 Cells metabolism, Hypersensitivity, Immediate immunology, Immunity, Th2 Cells immunology
- Abstract
Background: Although most children with asthma and rhinitis are sensitized to aeroallergens, only a minority of sensitized children are symptomatic, implying the underlying operation of efficient anti-inflammatory control mechanisms., Objective: We sought to identify endogenous control mechanisms that attenuate expression of IgE-associated responsiveness to aeroallergens in sensitized children., Methods: In 3 independent population samples we analyzed relationships between aeroallergen-specific IgE and corresponding allergen-specific IgG (sIgG) and associated immunophenotypes in atopic children and susceptibility to asthma and rhinitis, focusing on responses to house dust mite and grass., Results: Among mite-sensitized children across all populations and at different ages, house dust mite-specific IgG/IgE ratios (but not IgG4/IgE ratios) were significantly lower in children with asthma compared with ratios in those without asthma and lowest among the most severely symptomatic. This finding was mirrored by relationships between rhinitis and antibody responses to grass. Depending on age/allergen specificity, 20% to 40% of children with allergen-specific IgE (sIgE) of 0.35 kU/L or greater had negative skin test responses, and these children also expressed the high sIgG/sIgE immunophenotype. sIgG1 from these children inhibited allergen-induced IgE-dependent basophil activation in a dose-dependent fashion. Profiling of aeroallergen-specific CD4(+) TH memory responses revealed positive associations between sIgG/sIgE ratios and IL-10-dependent gene signatures and significantly higher IL-10/TH2 cytokine (protein) ratios among nonsymptomatic children., Conclusion: In addition to its role in blocking TH2 effector activation in the late-phase allergic response, IL-10 is a known IgG1 switch factor. We posit that its production during allergen-induced memory responses contributes significantly to attenuation of inflammation through promoting IgG1-mediated damping of the FcεRI-dependent acute-phase reaction. sIgG1/sIgE balance might represent a readily accessible therapeutic target for asthma/rhinitis control., (Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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