Vectorized Scenario Description and Motion Prediction for Scenario-Based Testing

Automated vehicles (AVs) are tested in diverse scenarios, typically specified by parameters such as velocities, distances, or curve radii. To describe scenarios uniformly independent of such parameters, this paper proposes a vectorized scenario description defined by the road geometry and vehicles' trajectories. Data of this form are generated for three scenarios, merged, and used to train the motion prediction model VectorNet, allowing to predict an AV's trajectory for unseen scenarios. Predicting scenario evaluation metrics, VectorNet partially achieves lower errors than regression models that separately process the three scenarios' data. However, for comprehensive generalization, sufficient variance in the training data must be ensured. Thus, contrary to existing methods, our proposed method can merge diverse scenarios' data and exploit spatial and temporal nuances in the vectorized scenario description. As a result, data from specified test scenarios and real-world scenarios can be compared and combined for (predictive) analyses and scenario selection.Comment: 6 pages, 7 figures, 3 table

Transfer Importance Sampling \unicode{x2013} How Testing Automated Vehicles in Multiple Test Setups Helps With the Bias-Variance Tradeoff

The promise of increased road safety is a key motivator for the development of automated vehicles (AV). Yet, demonstrating that an AV is as safe as, or even safer than, a human-driven vehicle has proven to be challenging. Should an AV be examined purely virtually, allowing large numbers of fully controllable tests? Or should it be tested under real environmental conditions on a proving ground? Since different test setups have different strengths and weaknesses, it is still an open question how virtual and real tests should be combined. On the way to answer this question, this paper proposes transfer importance sampling (TIS), a risk estimation method linking different test setups. Fusing the concepts of transfer learning and importance sampling, TIS uses a scalable, cost-effective test setup to comprehensively explore an AV's behavior. The insights gained then allow parameterizing tests in a more trustworthy test setup accurately reflecting risks. We show that when using a trustworthy test setup alone is prohibitively expensive, linking it to a scalable test setup can increase efficiency \unicode{x2013} without sacrificing the result's validity. Thus, the test setups' individual deficiencies are compensated for by their systematic linkage.Comment: 6 pages, 5 figures, 1 table, submitted to IEEE ITSC 202

Optimal Treatment Strategies in the Context of ‘Treatment for Prevention’ against HIV-1 in Resource-Poor Settings

An estimated 2.7 million new HIV-1 infections occurred in 2010. `Treatment- for-prevention’ may strongly prevent HIV-1 transmission. The basic idea is that immediate treatment initiation rapidly decreases virus burden, which reduces the number of transmittable viruses and thereby the probability of infection. However, HIV inevitably develops drug resistance, which leads to virus rebound and nullifies the effect of `treatment-for-prevention’ for the time it remains unrecognized. While timely conducted treatment changes may avert periods of viral rebound, necessary treatment options and diagnostics may be lacking in resource-constrained settings. Within this work, we provide a mathematical platform for comparing different treatment paradigms that can be applied to many medical phenomena. We use this platform to optimize two distinct approaches for the treatment of HIV-1: (i) a diagnostic-guided treatment strategy, based on infrequent and patient-specific diagnostic schedules and (ii) a pro-active strategy that allows treatment adaptation prior to diagnostic ascertainment. Both strategies are compared to current clinical protocols (standard of care and the HPTN052 protocol) in terms of patient health, economic means and reduction in HIV-1 onward transmission exemplarily for South Africa. All therapeutic strategies are assessed using a coarse-grained stochastic model of within-host HIV dynamics and pseudo-codes for solving the respective optimal control problems are provided. Our mathematical model suggests that both optimal strategies (i)-(ii) perform better than the current clinical protocols and no treatment in terms of economic means, life prolongation and reduction of HIV-transmission. The optimal diagnostic-guided strategy suggests rare diagnostics and performs similar to the optimal pro-active strategy. Our results suggest that ‘treatment-for-prevention’ may be further improved using either of the two analyzed treatment paradigms

Probabilistic Metamodels for an Efficient Characterization of Complex Driving Scenarios

To validate the safety of automated vehicles (AV), scenario-based testing aims to systematically describe driving scenarios an AV might encounter. In this process, continuous inputs such as velocities result in an infinite number of possible variations of a scenario. Thus, metamodels are used to perform analyses or to select specific variations for examination. However, despite the safety criticality of AV testing, metamodels are usually seen as a part of an overall approach, and their predictions are not questioned. This paper analyzes the predictive performance of Gaussian processes (GP), deep Gaussian processes, extra-trees, and Bayesian neural networks (BNN), considering four scenarios with 5 to 20 inputs. Building on this, an iterative approach is introduced and evaluated, which allows to efficiently select test cases for common analysis tasks. The results show that regarding predictive performance, the appropriate selection of test cases is more important than the choice of metamodels. However, the choice of metamodels remains crucial: Their great flexibility allows BNNs to benefit from large amounts of data and to model even the most complex scenarios. In contrast, less flexible models like GPs convince with higher reliability. Hence, relevant test cases are best explored using scalable virtual test setups and flexible models. Subsequently, more realistic test setups and more reliable models can be used for targeted testing and validation.Comment: 10 pages, 14 figures, 1 table, associated dataset at https://github.com/wnklmx/DSIO

Biological and clinical insights from genetics of insomnia symptoms

Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes. The underlying pathophysiological processes and causal relationships of insomnia with disease are poorly understood. Here we identified 57 loci for self-reported insomnia symptoms in the UK Biobank (n = 453,379) and confirmed their effects on self-reported insomnia symptoms in the HUNT Study (n = 14,923 cases and 47,610 controls), physician-diagnosed insomnia in the Partners Biobank (n = 2,217 cases and 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n = 83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis and of genes expressed in multiple brain regions, skeletal muscle, and adrenal glands. Evidence of shared genetic factors was found between frequent insomnia symptoms and restless legs syndrome, aging, and cardiometabolic, behavioral, psychiatric, and reproductive traits. Evidence was found for a possible causal link between insomnia symptoms and coronary artery disease, depressive symptoms, and subjective well-being

RANTES/CCL5 and Risk for Coronary Events: Results from the MONICA/KORA Augsburg Case-Cohort, Athero-Express and CARDIoGRAM Studies

BACKGROUND: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. METHODS AND FINDINGS: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±4.8 years). Cox proportional hazard models adjusting for age, sex, body mass index, metabolic factors and lifestyle factors revealed no significant association between RANTES and incident coronary events (HR [95% CI] for increasing RANTES tertiles 1.0, 1.03 [0.75-1.42] and 1.11 [0.81-1.54]). None of six CCL5 single nucleotide polymorphisms and no common haplotype showed significant associations with coronary events. Also in the CARDIoGRAM study (>22,000 cases, >60,000 controls), none of these CCL5 SNPs was significantly associated with coronary artery disease. In the prospective Athero-Express biobank study, RANTES plaque levels were measured in 606 atherosclerotic lesions from patients who underwent carotid endarterectomy. RANTES content in atherosclerotic plaques was positively associated with macrophage infiltration and inversely associated with plaque calcification. However, there was no significant association between RANTES content in plaques and risk for coronary events (mean follow-up 2.8±0.8 years). CONCLUSIONS: High RANTES plaque levels were associated with an unstable plaque phenotype. However, the absence of associations between (i) RANTES serum levels, (ii) CCL5 genotypes and (iii) RANTES content in carotid plaques and either coronary artery disease or incident coronary events in our cohorts suggests that RANTES may not be a novel coronary risk biomarker. However, the potential relevance of RANTES levels in platelet-poor plasma needs to be investigated in further studies

Embracing monogenic Parkinson's disease: the MJFF Global Genetic PD Cohort

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Michael J. Fox Foundation for Parkinson's Research. Grant Number: ID 15015.02. NIHR Cambridge Biomedical Research Centre. Grant Number: BRC-1215-20014info:eu-repo/semantics/publishedVersio

RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies

Background: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. Methods and Findings: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±