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Several important aspects related to SARS-CoV-2 transmission are not well known due to a lack of appropriate data. However, mathematical and computational tools can be used to extract part of this information from the available data, like some hidden age-related characteristics. In this paper, we investigate age-specific differences in susceptibility to and infectiousness upon contracting SARS-CoV-2 infection. More specifically, we use panel-based social contact data from diary-based surveys conducted in Belgium combined with the next generation principle to infer the relative incidence and we compare this to real-life incidence data. Comparing these two allows for the estimation of age-specific transmission parameters. Our analysis implies the susceptibility in children to be around half of the susceptibility in adults, and even lower for very young children (preschooler). However, the probability of adults and the elderly to contract the infection is decreasing throughout the vaccination campaign, thereby modifying the picture over time.

This paper presents a protocol, or design, for the analysis of a comparative effectiveness evaluation of abiraterone acetate against enzalutamide, two drugs given to prostate cancer patients. The design explicitly make use of differences in prescription practices across 21 Swedish county councils for the estimation of the two drugs comparative effectiveness on overall mortality, pain and skeleton related events. The design requires that the county factor: (1) affects the probability to be treated (i.e. being prescribed abiraterone acetate instead of enzalutamide) but (2) is not otherwise correlated with the outcome. The fist assumption is validated in the data. The latter assumption may be untenable and also not possible to formally test. However, the validity of this assumption is evaluated in a sensitivity analysis, where data on the two morbidity outcomes (i.e. pain and skeleton related events) observed before prescription date are used. We find that the county factor does \emph{not} explain these two pre-measured outcomes. The implication is that we cannot reject the validity of the design.

The Covid-19 pandemic presents a serious threat to people's health, resulting in over 250 million confirmed cases and over 5 million deaths globally. In order to reduce the burden on national health care systems and to mitigate the effects of the outbreak, accurate modelling and forecasting methods for short- and long-term health demand are needed to inform government interventions aiming at curbing the pandemic. Current research on Covid-19 is typically based on a single source of information, specifically on structured historical pandemic data. Other studies are exclusively focused on unstructured online retrieved insights, such as data available from social media. However, the combined use of structured and unstructured information is still uncharted. This paper aims at filling this gap, by leveraging historical as well as social media information with a novel data integration methodology. The proposed approach is based on vine copulas, which allow us to improve predictions by exploiting the dependencies between different sources of information. We apply the methodology to combine structured datasets retrieved from official sources and to a big unstructured dataset of information collected from social media. The results show that the proposed approach, compared to traditional approaches, yields more accurate estimations and predictions of the evolution of the Covid-19 pandemic.

Inference of directed relations given some unspecified interventions, that is, the target of each intervention is not known, is important yet challenging. For instance, it is of high interest to unravel the regulatory roles of genes with inherited genetic variants like single-nucleotide polymorphisms (SNPs), which can be unspecified interventions because of their regulatory function on some unknown genes. In this article, we test hypothesized directed relations with unspecified interventions. First, we derive conditions to yield an identifiable model. Unlike classical inference, hypothesis testing requires identifying ancestral relations and relevant interventions for each hypothesis-specific primary variable, referring to as causal discovery. Towards this end, we propose a peeling algorithm to establish a hierarchy of primary variables as nodes, starting with leaf nodes at the hierarchy's bottom, for which we derive a difference-of-convex (DC) algorithm for nonconvex minimization. Moreover, we prove that the peeling algorithm yields consistent causal discovery, and the DC algorithm is a low-order polynomial algorithm capable of finding a global minimizer almost surely under the data generating distribution. Second, we propose a modified likelihood ratio test, eliminating nuisance parameters to increase power. To enhance finite-sample performance, we integrate the modified likelihood ratio test with a data perturbation scheme by accounting for the uncertainty of identifying ancestral relations and relevant interventions. Also, we show that the distribution of a data-perturbation test statistic converges to the target distribution in high dimensions. Numerical examples demonstrate the utility and effectiveness of the proposed methods, including an application to infer gene regulatory networks.

Longitudinal observational patient data can be used to investigate the causal effects of time-varying treatments on time-to-event outcomes. Several methods have been developed for controlling for the time-dependent confounding that typically occurs. The most commonly used is inverse probability weighted estimation of marginal structural models (MSM-IPTW). An alternative, the sequential trials approach, is increasingly popular, in particular in combination with the target trial emulation framework. This approach involves creating a sequence of `trials' from new time origins, restricting to individuals as yet untreated and meeting other eligibility criteria, and comparing treatment initiators and non-initiators. Individuals are censored when they deviate from their treatment status at the start of each `trial' (initiator/non-initiator) and this is addressed using inverse probability of censoring weights. The analysis is based on data combined across trials. We show that the sequential trials approach can estimate the parameter of a particular MSM, and compare it to a MSM-IPTW with respect to the estimands being identified, the assumptions needed and how data are used differently. We show how both approaches can estimate the same marginal risk differences. The two approaches are compared using a simulation study. The sequential trials approach, which tends to involve less extreme weights than MSM-IPTW, results in greater efficiency for estimating the marginal risk difference at most follow-up times, but this can, in certain scenarios, be reversed at late time points. We apply the methods to longitudinal observational data from the UK Cystic Fibrosis Registry to estimate the effect of dornase alfa on survival.

We propose a new problem setting to study the sequential interactions between a recommender system and a user. Instead of assuming the user is omniscient, static, and explicit, as the classical practice does, we sketch a more realistic user behavior model, under which the user: 1) rejects recommendations if they are clearly worse than others; 2) updates her utility estimation based on rewards from her accepted recommendations; 3) withholds realized rewards from the system. We formulate the interactions between the system and such an explorative user in a $K$-armed bandit framework and study the problem of learning the optimal recommendation on the system side. We show that efficient system learning is still possible but is more difficult. In particular, the system can identify the best arm with probability at least $1-\delta$ within $O(1/\delta)$ interactions, and we prove this is tight. Our finding contrasts the result for the problem of best arm identification with fixed confidence, in which the best arm can be identified with probability $1-\delta$ within $O(\log(1/\delta))$ interactions. This gap illustrates the inevitable cost the system has to pay when it learns from an explorative user's revealed preferences on its recommendations rather than from the realized rewards.

In health cohort studies, repeated measures of markers are often used to describe the natural history of a disease. Joint models allow to study their evolution by taking into account the possible informative dropout usually due to clinical events. However, joint modeling developments mostly focused on continuous Gaussian markers while, in an increasing number of studies, the actual marker of interest is non-directly measurable; it consitutes a latent quantity evaluated by a set of observed indicators from questionnaires or measurement scales. Classical examples include anxiety, fatigue, cognition. In this work, we explain how joint models can be extended to the framework of a latent quantity measured over time by markers of different nature (e.g. continuous, binary, ordinal). The longitudinal submodel describes the evolution over time of the quantity of interest defined as a latent process in a structural mixed model, and links the latent process to each marker repeated observation through appropriate measurement models. Simultaneously, the risk of multi-cause event is modelled via a proportional cause-specific hazard model that includes a function of the mixed model elements as linear predictor to take into account the association between the latent process and the risk of event. Estimation, carried out in the maximum likelihood framework and implemented in the R-package JLPM, has been validated by simulations. The methodology is illustrated in the French cohort on Multiple-System Atrophy (MSA), a rare and fatal neurodegenerative disease, with the study of dysphagia progression over time truncated by the occurrence of death.

Multi-modal word semantics aims to enhance embeddings with perceptual input, assuming that human meaning representation is grounded in sensory experience. Most research focuses on evaluation involving direct visual input, however, visual grounding can contribute to linguistic applications as well. Another motivation for this paper is the growing need for more interpretable models and for evaluating model efficiency regarding size and performance. This work explores the impact of visual information for semantics when the evaluation involves no direct visual input, specifically semantic similarity and relatedness. We investigate a new embedding type in-between linguistic and visual modalities, based on the structured annotations of Visual Genome. We compare uni- and multi-modal models including structured, linguistic and image based representations. We measure the efficiency of each model with regard to data and model size, modality / data distribution and information gain. The analysis includes an interpretation of embedding structures. We found that this new embedding conveys complementary information for text based embeddings. It achieves comparable performance in an economic way, using orders of magnitude less resources than visual models.

Recent years have witnessed the enormous success of low-dimensional vector space representations of knowledge graphs to predict missing facts or find erroneous ones. Currently, however, it is not yet well-understood how ontological knowledge, e.g. given as a set of (existential) rules, can be embedded in a principled way. To address this shortcoming, in this paper we introduce a framework based on convex regions, which can faithfully incorporate ontological knowledge into the vector space embedding. Our technical contribution is two-fold. First, we show that some of the most popular existing embedding approaches are not capable of modelling even very simple types of rules. Second, we show that our framework can represent ontologies that are expressed using so-called quasi-chained existential rules in an exact way, such that any set of facts which is induced using that vector space embedding is logically consistent and deductively closed with respect to the input ontology.

Generative Adversarial Networks (GAN) have shown great promise in tasks like synthetic image generation, image inpainting, style transfer, and anomaly detection. However, generating discrete data is a challenge. This work presents an adversarial training based correlated discrete data (CDD) generation model. It also details an approach for conditional CDD generation. The results of our approach are presented over two datasets; job-seeking candidates skill set (private dataset) and MNIST (public dataset). From quantitative and qualitative analysis of these results, we show that our model performs better as it leverages inherent correlation in the data, than an existing model that overlooks correlation.