Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

A Bayesian approach for place recognition

This paper presents a robust place recognition algorithm for mobile robots. The framework proposed combines nonlinear dimensionality reduction, nonlinear regression under noise, and variational Bayesian learning to create consistent probabilistic representations of places from images. These generative models are learnt from a few images and used for multi-class place recognition where classification is computed from a set of feature-vectors. Recognition can be performed in near real-time and accounts for complexity such as changes in illumination, occlusions and blurring. The algorithm was tested with a mobile robot in indoor and outdoor environments with sequences of 1579 and 3820 images respectively. This framework has several potential applications such as map building, autonomous navigation, search-rescue tasks and context recognition

Sequential nonlinear manifold learning

The computation of compact and meaningful representations of high dimensional sensor data has recently been addressed through the development of Nonlinear Dimensional Reduction (NLDR) algorithms. The numerical implementation of spectral NLDR techniques typically leads to a symmetric eigenvalue problem that is solved by traditional batch eigensolution algorithms. The application of such algorithms in real-time systems necessitates the development of sequential algorithms that perform feature extraction online. This paper presents an efficient online NLDR scheme, Sequential-Isomap, based on incremental singular value decomposition (SVD) and the Isomap method. Example simulations demonstrate the validity and significant potential of this technique in real-time applications such as autonomous systems

A statistical framework for natural feature representation

This paper presents a robust stochastic framework for the incorporation of visual observations into conventional estimation, data fusion, navigation and control algorithms. The representation combines Isomap, a non-linear dimensionality reduction algorithm, with expectation maximization, a statistical learning scheme. The joint probability distribution of this representation is computed offline based on existing training data. The training phase of the algorithm results in a nonlinear and non-Gaussian likelihood model of natural features conditioned on the underlying visual states. This generative model can be used online to instantiate likelihoods corresponding to observed visual features in real-time. The instantiated likelihoods are expressed as a Gaussian mixture model and are conveniently integrated within existing non-linear filtering algorithms. Example applications based on real visual data from heterogenous, unstructured environments demonstrate the versatility of the generative models

Learning articulated motion structures with Bayesian networks

This paper presents a general methodology for learning articulated motions that, despite having non-linear correlations, are cyclical and have a defined pattern of behavior Using conventional algorithms to extract features from images, a Bayesian classifier is applied to cluster and classify features of the moving object. Clusters are then associated in different frames and structure learning algorithms for Bayesian networks are used to recover the structure of the motion. This framework is applied to the human gait analysis and tracking but applications include any coordinated movement such as multi-robots behavior analysis

An information-theoretic approach to data fusion and sensor management

The use of multi-sensor systems entails a Data Fusion and Sensor Management requirement in order to optimize the use of resources and allow the synergistic operation of sensors. To date, data fusion and sensor management have largely been dealt with separately and primarily for centralized and hierarchical systems. Although work has recently been done in distributed and decentralized data fusion, very little of it has addressed sensor management. In decentralized systems, a consistent and coherent approach is essential and the ad hoc methods used in other systems become unsatisfactory. This thesis concerns the development of a unified approach to data fusion and sensor management in multi-sensor systems in general and decentralized systems in particular, within a single consistent information-theoretic framework. Our approach is based on considering information and its gain as the main goal of multi-sensor systems. We develop a probabilistic information update paradigm from which we derive directly architectures and algorithms for decentralized data fusion and, most importantly, address sensor management. Presented with several alternatives, the question of how to make decisions leading to the best sensing configuration or actions, defines the management problem. We discuss the issues in decentralized decision making and present a normative method for decentralized sensor management based on information as expected utility. We discuss several ways of realizing the solution culminating in an iterative method akin to bargaining for a general decentralized system. Underlying this is the need for a good sensor model detailing a sensor's physical operation and the phenomenological nature of measurements vis-a-vis the probabilistic information the sensor provides. Also, implicit in a sensor management problem is the existence of several sensing alternatives such as those provided by agile or multi-mode sensors. With our application in mind, we detail such a sensor model for a novel Tracking Sonar with precisely these capabilities making it ideal for managed data fusion. As an application, we consider vehicle navigation, specifically localization and map-building. Implementation is on the OxNav vehicle (JTR) which we are currently developing. The results show, firstly, how with managed data fusion, localization is greatly speeded up compared to previous published work and secondly, how synergistic operation such as sensor-feature assignments, hand-off and cueing can be realised decentrally. This implementation provides new ways of addressing vehicle navigation, while the theoretical results are applicable to a variety of multi-sensing problems.</p

Validation gating for non-linear non-Gaussian target tracking

This paper develops a general theory of validation gating for non-linear non-Gaussian mod- els. Validation gates are used in target tracking to cull very unlikely measurement-to-track associa- tions, before remaining association ambiguities are handled by a more comprehensive (and expensive) data association scheme. The essential property of a gate is to accept a high percentage of correct associ- ations, thus maximising track accuracy, but provide a su±ciently tight bound to minimise the number of ambiguous associations. For linear Gaussian systems, the ellipsoidal vali- dation gate is standard, and possesses the statistical property whereby a given threshold will accept a cer- tain percentage of true associations. This property does not hold for non-linear non-Gaussian models. As a system departs from linear-Gaussian, the ellip- soid gate tends to reject a higher than expected pro- portion of correct associations and permit an excess of false ones. In this paper, the concept of the ellip- soidal gate is extended to permit correct statistics for the non-linear non-Gaussian case. The new gate is demonstrated by a bearing-only tracking example